Mouse models of ciliopathies: The state of the art

DMM Disease Models and Mechanisms

Volumn 5, Issue 3, 2012, Pages 299-312

  Norris, Dominic P ^a   Grimes, Daniel T ^a  

^a MRC MAMMALIAN GENETICS UNIT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

POLYCYSTIN 1; POLYCYSTIN 2; SONIC HEDGEHOG PROTEIN;

ALLELE; ALSTROM SYNDROME; BARDET BIEDL SYNDROME; CEREBROSPINAL FLUID FLOW; CHONDRODYSPLASIA; CILIARY DYSKINESIA; CILIARY MOTILITY; DYSOSTOSIS; EUKARYOTIC FLAGELLUM; FERTILITY; GENE DELETION; GENE LOCUS; HUMAN; INTRACELLULAR SIGNALING; JEUNE SYNDROME; JOUBERT SYNDROME; KIDNEY POLYCYSTIC DISEASE; LOSS OF FUNCTION MUTATION; LUNG CLEARANCE; MECKEL SYNDROME; MOUSE MUTANT; NEPHRONOPHTHISIS; NONHUMAN; NULL ALLELE; PHENOTYPE; PRIORITY JOURNAL; REVIEW;

ABNORMALITIES, MULTIPLE; ANIMALS; CILIA; DISEASE MODELS, ANIMAL; HUMANS; MICE; SENSE ORGANS; SIGNAL TRANSDUCTION; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84860769609     PISSN: 17548403     EISSN: 17548411     Source Type: Journal    
DOI: 10.1242/dmm.009340     Document Type: Review

References (150)

1. Abu-Safieh, L., Al-Anazi, S., Al-Abdi, L., Hashem, M., Alkuraya, H., Alamr, M., Sirelkhatim, M. O., Al-Hassnan, Z., Alkuraya, B., Mohamed, J. Y. et al. (2012). In search of triallelism in Bardet-Biedl syndrome. Eur. J. Hum. Genet. 20, 420-427.
2. Acevedo-Arozena, A., Wells, S., Potter, P., Kelly, M., Cox, R. D. and Brown, S. D. (2008). ENU mutagenesis, a way forward to understand gene function. Ann. Rev. Gen. Hum. Genet. 9, 49-69.
3. Arsov, T., Larter, C. Z., Nolan, C. J., Petrovsky, N., Goodnow, C. C., Teoh, N. C., Yeh, M. M. and Farrell, G. C. (2006a). Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice. Biochem. Biophys. Res. Comm. 342, 1152-1159.
4. Arsov, T., Silva, D. G., O'Bryan, M. K., Sainsbury, A., Lee, N. J., Kennedy, C., Manji, S. S., Nelms, K., Liu, C., Vinuesa, C. G. et al. (2006b). Fat aussie-a new Alstrom syndrome mouse showing a critical role for ALMS1 in obesity, diabetes, and spermatogenesis. Mol. Endocrinol. 20, 1610-1622. (Pubitemid 43967568)
5. Ashe, A., Butterfield, N. C., Town, L., Courtney, A. D., Cooper, A. N., Ferguson, C., Barry, R., Olsson, F., Liem, K. F., Jr, Parton, R. G. et al. (2012). Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies. Hum. Mol. Genet. 21, 1808-1823.
6. Attanasio, M., Uhlenhaut, N. H., Sousa, V. H., O'Toole, J. F., Otto, E., Anlag, K., Klugmann, C., Treier, A. C., Helou, J., Sayer, J. A. et al. (2007). Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. Nat. Genet. 39, 1018-1024. (Pubitemid 47185176)
7. Badano, J. L., Mitsuma, N., Beales, P. L. and Katsanis, N. (2006). The ciliopathies: an emerging class of human genetic disorders. Ann. Rev. Genomics Hum. Genet. 7, 125-148. (Pubitemid 44627925)
8. Baker, K. and Beales, P. L. (2009). Making sense of cilia in disease: the human ciliopathies. Am. J. Med. Genet. C Semin. Med. Genet. 151C, 281-295.
9. Baly, C., Aioun, J., Badonnel, K., Lacroix, M. C., Durieux, D., Schlegel, C., Salesse, R. and Caillol, M. (2007). Leptin and its receptors are present in the rat olfactory mucosa and modulated by the nutritional status. Brain Res. 1129, 130-141. (Pubitemid 46055256)
10. Berbari, N. F., O'Connor, A. K., Haycraft, C. J. and Yoder, B. K. (2009). The primary cilium as a complex signaling center. Curr. Biol. 19, R526-R535.
11. Bergmann, C., Fliegauf, M., Bruchle, N. O., Frank, V., Olbrich, H., Kirschner, J., Schermer, B., Schmedding, I., Kispert, A., Kranzlin, B. et al. (2008). Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia. Am. J. Hum. Genet. 82, 959-970.
12. Bimonte, S., De Angelis, A., Quagliata, L., Giusti, F., Tammaro, R., Dallai, R., Ascenzi, M. G., Diez-Roux, G. and Franco, B. (2011). Ofd1 is required in limb bud patterning and endochondral bone development. Dev. Biol. 349, 179-191.
13. Bloodgood, R. A. (2009). From central to rudimentary to primary: the history of an underappreciated organelle whose time has come. The primary cilium. Methods Cell Biol. 94, 3-52.
14. Bloodgood, R. A. (2010). Sensory reception is an attribute of both primary cilia and motile cilia. J. Cell Sci. 123, 505-509.
15. Burghes, A. H., Vaessin, H. E. and de la Chapelle, A. (2001). Genetics. The land between Mendelian and multifactorial inheritance. Science 293, 2213-2214.
16. Caspary, T., Larkins, C. E. and Anderson, K. V. (2007). The graded response to sonic hedgehog depends on cilia architecture. Dev. Cell 12, 767.
17. Chang, B., Khanna, H., Hawes, N., Jimeno, D., He, S., Lillo, C., Parapuram, S. K., Cheng, H., Scott, A., Hurd, R. E. et al. (2006). In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum. Mol. Genet. 15, 1847-1857. (Pubitemid 43821775)
18. Cheung, H. O., Zhang, X., Ribeiro, A., Mo, R., Makino, S., Puviindran, V., Law, K. K., Briscoe, J. and Hui, C. C. (2009). The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling. Sci. Signal. 2, ra29.
19. Chilvers, M. A., Rutman, A. and O'Callaghan, C. (2003). Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J. Allergy Clin. Immunol. 112, 518-524. (Pubitemid 37108555)
20. Christensen, S. T., Pedersen, L. B., Schneider, L. and Satir, P. (2007). Sensory cilia and integration of signal transduction in human health and disease. Traffic 8, 97-109. (Pubitemid 46099997)
21. Collin, G. B., Cyr, E., Bronson, R., Marshall, J. D., Gifford, E. J., Hicks, W., Murray, S. A., Zheng, Q. Y., Smith, R. S., Nishina, P. M. et al. (2005). Alms1-disrupted mice recapitulate human Alstrom syndrome. Hum. Mol. Genet. 14, 2323-2333. (Pubitemid 41417995)
22. Cui, C., Chatterjee, B., Francis, D., Yu, Q., SanAgustin, J. T., Francis, R., Tansey, T., Henry, C., Wang, B., Lemley, B. et al. (2011). Disruption of Mks1 localization to the mother centriole causes cilia defects and developmental malformations in Meckel- Gruber syndrome. Dis. Model. Mech. 4, 43-56.
23. Davenport, J. R., Watts, A. J., Roper, V. C., Croyle, M. J., van Groen, T., Wyss, J. M., Nagy, T. R., Kesterson, R. A. and Yoder, B. K. (2007). Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr. Biol. 17, 1586-1594. (Pubitemid 47380400)
24. Davis, R. E., Swiderski, R. E., Rahmouni, K., Nishimura, D. Y., Mullins, R. F., Agassandian, K., Philp, A. R., Searby, C. C., Andrews, M. P., Thompson, S. et al. (2007). A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Proc. Natl. Acad. Sci. USA 104, 19422-19427.
25. Dawe, H. R., Smith, U. M., Cullinane, A. R., Gerrelli, D., Cox, P., Badano, J. L., Blair- Reid, S., Sriram, N., Katsanis, N., Attie-Bitach, T. et al. (2007). The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation. Hum. Mol. Genet. 16, 173-186. (Pubitemid 46179000)
26. de Conciliis, L., Marchitiello, A., Wapenaar, M. C., Borsani, G., Giglio, S., Mariani, M., Consalez, G. G., Zuffardi, O., Franco, B., Ballabio, A. et al. (1998). Characterization of Cxorf5 (71-7A), a novel human cDNA mapping to Xp22 and encoding a protein containing coiled-coil alpha-helical domains. Genomics 51, 243-250.
27. Dowdle, W. E., Robinson, J. F., Kneist, A., Sirerol-Piquer, M. S., Frints, S. G., Corbit, K. C., Zaghloul, N. A., van Lijnschoten, G., Mulders, L., Verver, D. E. et al. (2011). Disruption of a ciliary B9 protein complex causes Meckel syndrome. Am. J. Hum. Genet. 89, 94-110.
28. Drummond, I. A. (2012). Cilia functions in development. Curr. Opin. Cell Biol. 24, 24-30.
29. Eggenschwiler, J. T. and Anderson, K. V. (2007). Cilia and developmental signaling. Annu. Rev. Cell Dev. Biol. 23, 345-373.
30. Eichers, E. R., Abd-El-Barr, M. M., Paylor, R., Lewis, R. A., Bi, W., Lin, X., Meehan, T. P., Stockton, D. W., Wu, S. M., Lindsay, E. et al. (2006). Phenotypic characterization of Bbs4 null mice reveals age-dependent penetrance and variable expressivity. Hum. Genet. 120, 211-226. (Pubitemid 44204010)
31. Eley, L., Gabrielides, C., Adams, M., Johnson, C. A., Hildebrandt, F. and Sayer, J. A. (2008). Jouberin localizes to collecting ducts and interacts with nephrocystin-1. Kidney Int. 74, 1139-1149.
32. Ermakov, A., Stevens, J. L., Whitehill, E., Robson, J. E., Pieles, G., Brooker, D., Goggolidou, P., Powles-Glover, N., Hacker, T., Young, S. R. et al. (2009). Mouse mutagenesis identifies novel roles for left-right patterning genes in pulmonary, craniofacial, ocular, and limb development. Dev. Dyn. 238, 581-594.
33. Ezratty, E. J., Stokes, N., Chai, S., Shah, A. S., Williams, S. E. and Fuchs, E. (2011). A role for the primary cilium in Notch signaling and epidermal differentiation during skin development. Cell 145, 1129-1141.
34. Fath, M. A., Mullins, R. F., Searby, C., Nishimura, D. Y., Wei, J., Rahmouni, K., Davis, R. E., Tayeh, M. K., Andrews, M., Yang, B. et al. (2005). Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome. Hum. Mol. Genet. 14, 1109-1118. (Pubitemid 40613900)
35. Ferrante, M. I., Giorgio, G., Feather, S. A., Bulfone, A., Wright, V., Ghiani, M., Selicorni, A., Gammaro, L., Scolari, F., Woolf, A. S. et al. (2001). Identification of the gene for oral-facial-digital type I syndrome. Am. J. Hum. Genet. 68, 569-576. (Pubitemid 32202752)
36. Ferrante, M. I., Barra, A., Truong, J. P., Banfi, S., Disteche, C. M. and Franco, B. (2003). Characterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant. Genomics 81, 560-569. (Pubitemid 36627500)
37. Ferrante, M. I., Zullo, A., Barra, A., Bimonte, S., Messaddeq, N., Studer, M., Dolle, P. and Franco, B. (2006). Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat. Genet. 38, 112-117. (Pubitemid 43011891)
38. Field, S., Riley, K. L., Grimes, D. T., Hilton, H., Simon, M., Powles-Glover, N., Siggers, P., Bogani, D., Greenfield, A. and Norris, D. P. (2011). Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2. Development 138, 1131-1142.
39. Fliegauf, M., Benzing, T. and Omran, H. (2007). When cilia go bad: cilia defects and ciliopathies. Nat. Rev. Mol. Cell Biol. 8, 880-893. (Pubitemid 47622564)
40. Forman, J. R., Qamar, S., Paci, E., Sandford, R. N. and Clarke, J. (2005). The remarkable mechanical strength of polycystin-1 supports a direct role in mechanotransduction. J. Mol. Biol. 349, 861-871. (Pubitemid 40725959)
41. Frank, V., Ortiz Bruchle, N., Mager, S., Frints, S. G., Bohring, A., du Bois, G., Debatin, I., Seidel, H., Senderek, J., Besbas, N. et al. (2007). Aberrant splicing is a common mutational mechanism in MKS1, a key player in Meckel-Gruber syndrome. Hum. Mutat. 28, 638-639.
42. Fuchs, H., Gailus-Durner, V., Adler, T., Aguilar-Pimentel, J. A., Becker, L., Calzada- Wack, J., Da Silva-Buttkus, P., Neff, F., Gotz, A., Hans, W. et al. (2011). Mouse phenotyping. Methods 53, 120-135.
43. Garcia-Garcia, M. J., Eggenschwiler, J. T., Caspary, T., Alcorn, H. L., Wyler, M. R., Huangfu, D., Rakeman, A. S., Lee, J. D., Feinberg, E. H., Timmer, J. R. et al. (2005). Analysis of mouse embryonic patterning and morphogenesis by forward genetics. Proc. Natl. Acad. Sci. USA 102, 5913-5919. (Pubitemid 40594229)
44. Garcia-Gonzalo, F. R., Corbit, K. C., Sirerol-Piquer, M. S., Ramaswami, G., Otto, E. A., Noriega, T. R., Seol, A. D., Robinson, J. F., Bennett, C. L., Josifova, D. J. et al. (2011). A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat. Genet. 43, 776-784.
45. Gates, H., Mallon, A. M. and Brown, S. D. (2011). High-throughput mouse phenotyping. Methods 53, 394-404.
46. Gattone, V. H., 2nd, Wang, X., Harris, P. C. and Torres, V. E. (2003). Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat. Med. 9, 1323-1326. (Pubitemid 37279858)
47. Goetz, S. C. and Anderson, K. V. (2010). The primary cilium: a signalling centre during vertebrate development. Nat. Rev. Genet. 11, 331-344.
48. Gondo, Y. (2008). Trends in large-scale mouse mutagenesis: from genetics to functional genomics. Nat. Rev. Genet. 9, 803-810.
49. Guo, D. F., Beyer, A. M., Yang, B., Nishimura, D. Y., Sheffield, V. C. and Rahmouni, K. (2011). Inactivation of Bardet-Biedl syndrome genes causes kidney defects. Am. J. Physiol. Renal Physiol. 300, F574-F580.
50. Hanaoka, K., Qian, F., Boletta, A., Bhunia, A. K., Piontek, K., Tsiokas, L., Sukhatme, V. P., Guggino, W. B. and Germino, G. G. (2000). Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature 408, 990-994. (Pubitemid 32101647)
51. Harris, P. C. and Torres, V. E. (2009). Polycystic kidney disease. Annu. Rev. Med. 60, 321-337.
52. Haycraft, C. J., Zhang, Q., Song, B., Jackson, W. S., Detloff, P. J., Serra, R. and Yoder, B. K. (2007). Intraflagellar transport is essential for endochondral bone formation. Development 134, 307-316.
53. Hsiao, Y. C., Tong, Z. J., Westfall, J. E., Ault, J. G., Page-McCaw, P. S. and Ferland, R. J. (2009). Ahi1, whose human ortholog is mutated in Joubert syndrome, is required for Rab8a localization, ciliogenesis and vesicle trafficking. Hum. Mol. Genet. 18, 3926-3941.
54. Huangfu, D. and Anderson, K. V. (2005). Cilia and Hedgehog responsiveness in the mouse. Proc. Natl. Acad. Sci. USA 102, 11325-11330. (Pubitemid 41153819)
55. Huangfu, D., Liu, A., Rakeman, A. S., Murcia, N. S., Niswander, L. and Anderson, K. V. (2003). Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426, 83-87. (Pubitemid 37432545)
56. Ibanez-Tallon, I., Gorokhova, S. and Heintz, N. (2002). Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus. Hum. Mol. Genet. 11, 715-721. (Pubitemid 34285143)
57. Insinna, C. and Besharse, J. C. (2008). Intraflagellar transport and the sensory outer segment of vertebrate photoreceptors. Dev. Dyn. 237, 1982-1992.
58. Ishizuka, K., Kamiya, A., Oh, E. C., Kanki, H., Seshadri, S., Robinson, J. F., Murdoch, H., Dunlop, A. J., Kubo, K., Furukori, K. et al. (2011). DISC1-dependent switch from progenitor proliferation to migration in the developing cortex. Nature 473, 92-96.
59. Jacoby, M., Cox, J. J., Gayral, S., Hampshire, D. J., Ayub, M., Blockmans, M., Pernot, E., Kisseleva, M. V., Compere, P., Schiffmann, S. N. et al. (2009). INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat. Genet. 41, 1027-1031.
60. Jagger, D., Collin, G., Kelly, J., Towers, E., Nevill, G., Longo-Guess, C., Benson, J., Halsey, K., Dolan, D., Marshall, J. et al. (2011). Alstrom Syndrome protein ALMS1 localizes to basal bodies of cochlear hair cells and regulates cilium-dependent planar cell polarity. Hum. Mol. Genet. 20, 466-481.
61. Jiang, S. T., Chiou, Y. Y., Wang, E., Lin, H. K., Lee, S. P., Lu, H. Y., Wang, C. K., Tang, M. J. and Li, H. (2008). Targeted disruption of Nphp1 causes male infertility due to defects in the later steps of sperm morphogenesis in mice. Hum. Mol. Genet. 17, 3368-3379.
62. Jiang, S. T., Chiou, Y. Y., Wang, E., Chien, Y. L., Ho, H. H., Tsai, F. J., Lin, C. Y., Tsai, S. P. and Li, H. (2009). Essential role of nephrocystin in photoreceptor intraflagellar transport in mouse. Hum. Mol. Genet. 18, 1566-1577.
63. Jin, H. and Nachury, M. V. (2009). The BBSome. Curr. Biol. 19, R472-R473.
64. Jin, H., White, S. R., Shida, T., Schulz, S., Aguiar, M., Gygi, S. P., Bazan, J. F. and Nachury, M. V. (2010). The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia. Cell 141, 1208-1219.
65. Karcher, C., Fischer, A., Schweickert, A., Bitzer, E., Horie, S., Witzgall, R. and Blum, M. (2005). Lack of a laterality phenotype in Pkd1 knock-out embryos correlates with absence of polycystin-1 in nodal cilia. Differentiation 73, 425-432.
66. Katsanis, N., Ansley, S. J., Badano, J. L., Eichers, E. R., Lewis, R. A., Hoskins, B. E., Scambler, P. J., Davidson, W. S., Beales, P. L. and Lupski, J. R. (2001). Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science 293, 2256-2259. (Pubitemid 32900235)
67. Keppler-Noreuil, K. M., Adam, M. P., Welch, J., Muilenburg, A. and Willing, M. C. (2011). Clinical insights gained from eight new cases and review of reported cases with Jeune syndrome (asphyxiating thoracic dystrophy). Am. J. Med. Genet. 155A, 1021-1032.
68. Khanna, H., Davis, E. E., Murga-Zamalloa, C. A., Estrada-Cuzcano, A., Lopez, I., den Hollander, A. I., Zonneveld, M. N., Othman, M. I., Waseem, N., Chakarova, C. F. et al. (2009). A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat. Genet. 41, 739-745.
69. Kim, Y. S., Kang, H. S., Herbert, R., Beak, J. Y., Collins, J. B., Grissom, S. F. and Jetten, A. M. (2008). Kruppel-like zinc finger protein Glis2 is essential for the maintenance of normal renal functions. Mol. Cell. Biol. 28, 2358-2367. (Pubitemid 351429981)
70. Kudryashova, E., Wu, J., Havton, L. A. and Spencer, M. J. (2009). Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component. Hum. Mol. Genet. 18, 1353-1367.
71. Kudryashova, E., Struyk, A., Mokhonova, E., Cannon, S. C. and Spencer, M. J. (2011). The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype. Hum. Mol. Genet. 20, 3925-3932.
72. Kulaga, H. M., Leitch, C. C., Eichers, E. R., Badano, J. L., Lesemann, A., Hoskins, B. E., Lupski, J. R., Beales, P. L., Reed, R. R. and Katsanis, N. (2004). Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat. Genet. 36, 994-998. (Pubitemid 39167497)
73. Lancaster, M. A., Louie, C. M., Silhavy, J. L., Sintasath, L., Decambre, M., Nigam, S. K., Willert, K. and Gleeson, J. G. (2009). Impaired Wnt-beta-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy. Nat. Med. 15, 1046-1054.
74. Lancaster, M. A., Gopal, D. J., Kim, J., Saleem, S. N., Silhavy, J. L., Louie, C. M., Thacker, B. E., Williams, Y., Zaki, M. S. and Gleeson, J. G. (2011). Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome. Nat. Med. 17, 726-731.
75. Larter, C. Z., Yeh, M. M., Van Rooyen, D. M., Teoh, N. C., Brooling, J., Hou, J. Y., Williams, J., Clyne, M., Nolan, C. J. and Farrell, G. C. (2009). Roles of adipose restriction and metabolic factors in progression of steatosis to steatohepatitis in obese, diabetic mice. J. Gastroenterol. Hepatol. 24, 1658-1668.
76. Lee, J. E., Silhavy, J. L., Zaki, M. S., Schroth, J., Bielas, S. L., Marsh, S. E., Olvera, J., Brancati, F., Iannicelli, M., Ikegami, K. et al. (2012). CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium. Nat. Genet. 44, 193-199.
77. Lee, T., Shah, C. and Xu, E. Y. (2007). Gene trap mutagenesis: a functional genomics approach towards reproductive research. Mol. Hum. Reprod. 13, 771-779. (Pubitemid 350131350)
78. Li, G., Vega, R., Nelms, K., Gekakis, N., Goodnow, C., McNamara, P., Wu, H., Hong, N. A. and Glynne, R. (2007). A role for Alstrom syndrome protein, alms1, in kidney ciliogenesis and cellular quiescence. PLoS Genet. 3, e8.
79. Liem, K. F., Jr, He, M., Ocbina, P. J. and Anderson, K. V. (2009). Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling. Proc. Natl. Acad. Sci. USA 106, 13377-13382.
80. Liu, S., Lu, W., Obara, T., Kuida, S., Lehoczky, J., Dewar, K., Drummond, I. A. and Beier, D. R. (2002). A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish. Development 129, 5839-5846. (Pubitemid 36054625)
81. Livraghi, A. and Randell, S. H. (2007). Cystic fibrosis and other respiratory diseases of impaired mucus clearance. Toxicol. Pathol. 35, 116-129. (Pubitemid 46328419)
82. Logan, C. V., Abdel-Hamed, Z. and Johnson, C. A. (2011). Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects. Mol. Neurobiol. 43, 12-26.
83. Louie, C. M., Caridi, G., Lopes, V. S., Brancati, F., Kispert, A., Lancaster, M. A., Schlossman, A. M., Otto, E. A., Leitges, M., Grone, H. J. et al. (2010). AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis. Nat. Genet. 42, 175-180.
84. Lucas, J. S., Adam, E. C., Goggin, P. M., Jackson, C. L., Powles-Glover, N., Patel, S. H., Humphreys, J., Fray, M. D., Falconnet, E., Blouin, J. L. et al. (2011). Static respiratory cilia associated with mutations in Dnahc11/DNAH11: A mouse model of PCD. Hum. Mutat. 33, 495-503.
85. Ma, L., Xu, M., Forman, J. R., Clarke, J. and Oberhauser, A. F. (2009). Naturally occurring mutations alter the stability of polycystin-1 polycystic kidney disease (PKD) domains. J. Biol. Chem. 284, 32942-32949.
86. Marshall, J. D., Maffei, P., Collin, G. B. and Naggert, J. K. (2011a). Alstrom syndrome: genetics and clinical overview. Curr. Genomics 12, 225-235.
87. Marshall, J. D., Maffei, P., Beck, S., Barrett, T. G. and Paisey, R. B. (2011b). Clinical utility gene card for: Alstrom syndrome. Eur. J. Hum. Genet. 19, doi: 10.1038/ejhg.2011.72
88. Marshall, W. F. and Nonaka, S. (2006). Cilia: tuning in to the cell's antenna. Curr. Biol. 16, R604-R614. (Pubitemid 44142993)
89. Marszalek, J. R., Ruiz-Lozano, P., Roberts, E., Chien, K. R. and Goldstein, L. S. (1999). Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. Proc. Natl. Acad. Sci. USA 96, 5043-5048. (Pubitemid 29214532)
90. McEwen, D. P., Koenekoop, R. K., Khanna, H., Jenkins, P. M., Lopez, I., Swaroop, A. and Martens, J. R. (2007). Hypomorphic CEP290/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons. Proc. Natl. Acad. Sci. USA 104, 15917-15922. (Pubitemid 350035399)
91. McGrath, J., Somlo, S., Makova, S., Tian, X. and Brueckner, M. (2003). Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114, 61-73. (Pubitemid 36859841)
92. McQuinn, T. C., Miga, D. E., Mjaatvedt, C. H., Phelps, A. L. and Wessels, A. (2001). Cardiopulmonary malformations in the inv/inv mouse. Anat. Rec. 263, 62-71.
93. Morgan, H., Beck, T., Blake, A., Gates, H., Adams, N., Debouzy, G., Leblanc, S., Lengger, C., Maier, H., Melvin, D. et al. (2010). EuroPhenome: a repository for high-throughput mouse phenotyping data. Nucleic Acids Res. 38, D577-D585.
94. Murdoch, J. N. and Copp, A. J. (2010). The relationship between sonic Hedgehog signaling, cilia, and neural tube defects. Birth Defects Res. A Clin. Mol. Teratol. 88, 633-652.
95. Mykytyn, K., Mullins, R. F., Andrews, M., Chiang, A. P., Swiderski, R. E., Yang, B., Braun, T., Casavant, T., Stone, E. M. and Sheffield, V. C. (2004). Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly. Proc. Natl. Acad. Sci. USA 101, 8664-8669. (Pubitemid 38745828)
96. Nauli, S. M., Alenghat, F. J., Luo, Y., Williams, E., Vassilev, P., Li, X., Elia, A. E., Lu, W., Brown, E. M., Quinn, S. J. et al. (2003). Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129-137. (Pubitemid 36177063)
97. Nishimura, D. Y., Fath, M., Mullins, R. F., Searby, C., Andrews, M., Davis, R., Andorf, J. L., Mykytyn, K., Swiderski, R. E., Yang, B. et al. (2004). Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. Proc. Natl. Acad. Sci. USA 101, 16588-16593. (Pubitemid 39557757)
98. Nonaka, S., Tanaka, Y., Okada, Y., Takeda, S., Harada, A., Kanai, Y., Kido, M. and Hirokawa, N. (1998). Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95, 829-837. (Pubitemid 29014462)
99. O'Toole, J. F., Otto, E. A., Frishberg, Y. and Hildebrandt, F. (2006). Retinitis pigmentosa and renal failure in a patient with mutations in INVS. Nephrol. Dial. Transplant. 21, 1989-1991. (Pubitemid 43985732)
100. Oberklaid, F., Danks, D. M., Mayne, V. and Campbell, P. (1977). Asphyxiating thoracic dysplasia. Clinical, radiological, and pathological information on 10 patients. Arch. Dis. Child. 52, 758-765. (Pubitemid 8218796)
101. Oh, E. C. and Katsanis, N. (2012). Cilia in vertebrate development and disease. Development 139, 443-448.
102. Okada, Y., Nonaka, S., Tanaka, Y., Saijoh, Y., Hamada, H. and Hirokawa, N. (1999). Abnormal nodal flow precedes situs inversus in iv and inv mice. Mol. Cell 4, 459-468. (Pubitemid 29531126)
103. Olbrich, H., Fliegauf, M., Hoefele, J., Kispert, A., Otto, E., Volz, A., Wolf, M. T., Sasmaz, G., Trauer, U., Reinhardt, R. et al. (2003). Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis. Nat. Genet. 34, 455-459. (Pubitemid 36935341)
104. Ostrowski, L. E., Yin, W., Rogers, T. D., Busalacchi, K. B., Chua, M., O'Neal, W. K. and Grubb, B. R. (2010). Conditional deletion of dnaic1 in a murine model of primary ciliary dyskinesia causes chronic rhinosinusitis. Am. J. Respir. Cell Mol. Biol. 43, 55-63.
105. Otto, E. A., Trapp, M. L., Schultheiss, U. T., Helou, J., Quarmby, L. M. and Hildebrandt, F. (2008). NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. J. Am. Soc. Nephrol. 19, 587-592. (Pubitemid 351355402)
106. Parisi, M. A. (2009). Clinical and molecular features of Joubert syndrome and related disorders. Am. J. Med. Genet. C Semin. Med. Genet. 151C, 326-340.
107. Pedersen, L. B., Veland, I. R., Schroder, J. M. and Christensen, S. T. (2008). Assembly of primary cilia. Dev. Dyn. 237, 1993-2006.
108. Pennekamp, P., Karcher, C., Fischer, A., Schweickert, A., Skryabin, B., Horst, J., Blum, M. and Dworniczak, B. (2002). The ion channel polycystin-2 is required for left-right axis determination in mice. Curr. Biol. 12, 938-943. (Pubitemid 34689231)
109. Piontek, K., Menezes, L. F., Garcia-Gonzalez, M. A., Huso, D. L. and Germino, G. G. (2007). A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat. Med. 13, 1490-1495. (Pubitemid 350224245)
110. Praetorius, H. A. and Spring, K. R. (2003). Removal of the MDCK cell primary cilium abolishes flow sensing. J. Membr. Biol. 191, 69-76. (Pubitemid 37011467)
111. Pretorius, P. R., Baye, L. M., Nishimura, D. Y., Searby, C. C., Bugge, K., Yang, B., Mullins, R. F., Stone, E. M., Sheffield, V. C. and Slusarski, D. C. (2010). Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform. PLoS Genet. 6, e1000884.
112. Quwailid, M. M., Hugill, A., Dear, N., Vizor, L., Wells, S., Horner, E., Fuller, S., Weedon, J., McMath, H., Woodman, P. et al. (2004). A gene-driven ENU-based approach to generating an allelic series in any gene. Mamm. Genome 15, 585-591. (Pubitemid 39050021)
113. Reiter, J. F. and Skarnes, W. C. (2006). Tectonic, a novel regulator of the Hedgehog pathway required for both activation and inhibition. Genes Dev. 20, 22-27. (Pubitemid 43042664)
114. Rix, S., Calmont, A., Scambler, P. J. and Beales, P. L. (2011). An Ift80 mouse model of short rib polydactyly syndromes shows defects in hedgehog signalling without loss or malformation of cilia. Hum. Mol. Genet. 20, 1306-1314.
115. Rosenbaum, J. L. and Witman, G. B. (2002). Intraflagellar transport. Nat. Rev. Mol. Cell Biol. 3, 813-825. (Pubitemid 35285272)
116. Ross, A. J., May-Simera, H., Eichers, E. R., Kai, M., Hill, J., Jagger, D. J., Leitch, C. C., Chapple, J. P., Munro, P. M., Fisher, S. et al. (2005). Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat. Genet. 37, 1135-1140. (Pubitemid 41486669)
117. Salomon, R., Saunier, S. and Niaudet, P. (2009). Nephronophthisis. Pediatr. Nephrol. 24, 2333-2344.
118. Sang, L., Miller, J. J., Corbit, K. C., Giles, R. H., Brauer, M. J., Otto, E. A., Baye, L. M., Wen, X., Scales, S. J., Kwong, M. et al. (2011). Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 145, 513-528.
119. Satir, P. and Christensen, S. T. (2007). Overview of structure and function of mammalian cilia. Annu. Rev. Physiol. 69, 377-400. (Pubitemid 46457649)
120. Sattar, S. and Gleeson, J. G. (2011). The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome-related disorders. Dev. Med. Child Neurol. 53, 793-798.
121. Schneider, L., Clement, C. A., Teilmann, S. C., Pazour, G. J., Hoffmann, E. K., Satir, P. and Christensen, S. T. (2005). PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr. Biol. 15, 1861-1866. (Pubitemid 41501522)
122. Seo, S., Guo, D. F., Bugge, K., Morgan, D. A., Rahmouni, K. and Sheffield, V. C. (2009). Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling. Hum. Mol. Genet. 18, 1323-1331.
123. Shah, A. S., Farmen, S. L., Moninger, T. O., Businga, T. R., Andrews, M. P., Bugge, K., Searby, C. C., Nishimura, D., Brogden, K. A., Kline, J. N. et al. (2008). Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia. Proc. Natl. Acad. Sci. USA 105, 3380-3385. (Pubitemid 351723561)
124. Sive, H. (2011). 'Model' or 'tool'? New definitions for translational research. Dis. Model. Mech. 4, 137-138.
125. Song, B., Haycraft, C. J., Seo, H. S., Yoder, B. K. and Serra, R. (2007). Development of the post-natal growth plate requires intraflagellar transport proteins. Dev. Biol. 305, 202-216. (Pubitemid 46589413)
126. Sugiyama, N. and Yokoyama, T. (2006). Sustained cell proliferation of renal epithelial cells in mice with inv mutation. Genes Cells 11, 1213-1224. (Pubitemid 44426209)
127. Tabin, C. J. and Vogan, K. J. (2003). A two-cilia model for vertebrate left-right axis specification. Genes Dev. 17, 1-6. (Pubitemid 36062503)
128. Tadenev, A. L., Kulaga, H. M., May-Simera, H. L., Kelley, M. W., Katsanis, N. and Reed, R. R. (2011). Loss of Bardet-Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting. Proc. Natl. Acad. Sci. USA 108, 10320-10325.
129. Takeda, S., Yonekawa, Y., Tanaka, Y., Okada, Y., Nonaka, S. and Hirokawa, N. (1999). Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis. J. Cell Biol. 145, 825-836. (Pubitemid 29240858)
130. Tan, S. Y., Rosenthal, J., Zhao, X. Q., Francis, R. J., Chatterjee, B., Sabol, S. L., Linask, K. L., Bracero, L., Connelly, P. S., Daniels, M. P. et al. (2007). Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia. J. Clin. Invest. 117, 3742-3752. (Pubitemid 350224085)
131. Tanaka, Y., Okada, Y. and Hirokawa, N. (2005). FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 435, 172-177. (Pubitemid 40685936)
132. Tobin, J. L. and Beales, P. L. (2007). Bardet-Biedl syndrome: beyond the cilium. Pediatr. Nephrol. 22, 926-936. (Pubitemid 46881909)
133. Toriello, H. V. (2009). Are the oral-facial-digital syndromes ciliopathies? Am. J. Med. Genet. A 149A, 1089-1095.
134. Town, T., Breunig, J. J., Sarkisian, M. R., Spilianakis, C., Ayoub, A. E., Liu, X., Ferrandino, A. F., Gallagher, A. R., Li, M. O., Rakic, P. et al. (2008). The stumpy gene is required for mammalian ciliogenesis. Proc. Natl. Acad. Sci. USA 105, 2853-2858. (Pubitemid 351723633)
135. Tran, P. V., Haycraft, C. J., Besschetnova, T. Y., Turbe-Doan, A., Stottmann, R. W., Herron, B. J., Chesebro, A. L., Qiu, H., Scherz, P. J., Shah, J. V. et al. (2008). THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat. Genet. 40, 403-410. (Pubitemid 351450878)
136. Valente, E. M., Logan, C. V., Mougou-Zerelli, S., Lee, J. H., Silhavy, J. L., Brancati, F., Iannicelli, M., Travaglini, L., Romani, S., Illi, B. et al. (2010). Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat. Genet. 42, 619-625.
137. Vierkotten, J., Dildrop, R., Peters, T., Wang, B. and Ruther, U. (2007). Ftm is a novel basal body protein of cilia involved in Shh signalling. Development 134, 2569-2577. (Pubitemid 47225954)
138. Wallingford, J. B. and Mitchell, B. (2011). Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev. 25, 201-213.
139. Waters, A. M. and Beales, P. L. (2011). Ciliopathies: an expanding disease spectrum. Pediatr. Nephrol. 26, 1039-1056.
140. Weatherbee, S. D., Niswander, L. A. and Anderson, K. V. (2009). A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling. Hum. Mol. Genet. 18, 4565-4575.
141. Westfall, J. E., Hoyt, C., Liu, Q., Hsiao, Y. C., Pierce, E. A.,
142. Wilson, P. D. (2008). Mouse models of polycystic kidney disease. Curr. Top. Dev. Biol. 84, 311-350.
143. Wolf, M. T. and Hildebrandt, F. (2011). Nephronophthisis. Pediatr. Nephrol. 26, 181-194.
144. Won, J., Marin de Evsikova, C., Smith, R. S., Hicks, W. L., Edwards, M. M., Longo- Guess, C., Li, T., Naggert, J. K. and Nishina, P. M. (2011). NPHP4 is necessary for normal photoreceptor ribbon synapse maintenance and outer segment formation, and for sperm development. Hum. Mol. Genet. 20, 482-496.
145. Wu, G., Tian, X., Nishimura, S., Markowitz, G. S., D'Agati, V., Park, J. H., Yao, L., Li, L., Geng, L., Zhao, H. et al. (2002). Trans-heterozygous Pkd1 and Pkd2 mutations modify expression of polycystic kidney disease. Hum. Mol. Genet. 11, 1845-1854.
146. Yokoyama, T., Copeland, N. G., Jenkins, N. A., Montgomery, C. A., Elder, F. F. and Overbeek, P. A. (1993). Reversal of left-right asymmetry: a situs inversus mutation. Science 260, 679-682. (Pubitemid 23167591)
147. Zaghloul, N. A. and Katsanis, N. (2009). Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy. J. Clin. Invest. 119, 428-437.
148. Zariwala, M. A., Omran, H. and Ferkol, T. W. (2011). The emerging genetics of primary ciliary dyskinesia. Proc. Am. Thorac. Soc. 8, 430-433.
149. Zhang, Q., Seo, S., Bugge, K., Stone, E. M. and Sheffield, V. C. (2012). BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes. Hum. Mol. Genet. doi: 10.1093/hmg/dds004
150. Zingman, L. V., Park, S., Olson, T. M., Alekseev, A. E. and Terzic, A. (2007). Aminoglycoside-induced translational read-through in disease: overcoming nonsense mutations by pharmacogenetic therapy. Clin. Pharmacol. Ther. 81, 99-103. (Pubitemid 46050873)