A knock-in mouse model for the R120G mutation of αB-crystallin recapitulates human hereditary myopathy and cataracts

PLoS ONE

Volumn 6, Issue 3, 2011, Pages

  Andley, Usha P ^a   Hamilton, Paul D ^b   Ravi, Nathan ^a,b   Weihl, Conrad C ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA CRYSTALLIN; DESMIN; VIMENTIN; CRYSTALLIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CATARACT; CONTROLLED STUDY; DISEASE COURSE; DISEASE SEVERITY; GEL PERMEATION CHROMATOGRAPHY; GENE DOSAGE; GENETIC DISORDER; HETEROZYGOTE; HOMOZYGOTE; IMMUNOASSAY; IMMUNOFLUORESCENCE TEST; IMMUNOPRECIPITATION; KNOCKOUT MOUSE; MISSENSE MUTATION; MOLECULAR PATHOLOGY; MOUSE; MOUSE MUTANT; MYOPATHY; NONHUMAN; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; SLIT LAMP; UBIQUITINATION; UPREGULATION; ANIMAL; DISEASE MODEL; GENE TARGETING; GENETIC PREDISPOSITION; GENETICS; HUMAN; MUSCLE DISEASE; MUTATION;

MUS;

ANIMALS; CATARACT; CRYSTALLINS; DISEASE MODELS, ANIMAL; GENE KNOCK-IN TECHNIQUES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MICE; MICE, MUTANT STRAINS; MUSCULAR DISEASES; MUTATION;

EID: 79952785522     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0017671     Document Type: Article

References (60)

1. Kappe G, Franck E, Verschuure P, Boelens WC, Leunissen JA, et al. (2003) The human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones 8: 53-61.
2. Horwitz J, (2003) Alpha-crystallin. Exp Eye Res 76: 145-153.
3. Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C, et al. (2004) Ageing and vision: structure, stability and function of lens crystallins. Prog Biophys Mol Biol 86: 407-485.
4. Bhat SP, Nagineni CN, (1989) alpha B subunit of lens-specific protein alpha-crystallin is present in other ocular and non-ocular tissues. Biochem Biophys Res Commun 158: 319-325.
5. Horwitz J, (1992) Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci U S A 89: 10449-10453.
6. Andley UP, Song Z, Wawrousek EF, Brady JP, Bassnett S, et al. (2001) Lens epithelial cells derived from alphaB-crystallin knockout mice demonstrate hyperproliferation and genomic instability. Faseb J 15: 221-229.
7. Sax CM, Piatigorsky J, (1994) Expression of the alpha-crystallin/small heat-shock protein/molecular chaperone genes in the lens and other tissues. Adv Enzymol Relat Areas Mol Biol 69: 155-201.
8. Brady JP, Garland DL, Green DE, Tamm ER, Giblin FJ, et al. (2001) AlphaB-crystallin in lens development and muscle integrity: a gene knockout approach. Invest Ophthalmol Vis Sci 42: 2924-2934.
9. Ousman SS, Tomooka BH, van Noort JM, Wawrousek EF, O'Conner K, et al. (2007) Protective and therapeutic role for alphaB-crystallin in autoimmune demyelination. Nature 448: 474-479.
10. Head MW, Goldman JE, (2000) Small heat shock proteins, the cytoskeleton, and inclusion body formation. Neuropathol Appl Neurobiol 26: 304-312.
11. Muchowski PJ, Wacker JL, (2005) Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci 6: 11-22.
12. Vicart P, Caron A, Guicheney P, Li Z, Prevost MC, et al. (1998) A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20: 92-95.
13. Sitterding SM, Wiseman WR, Schiller CL, Luan C, Chen F, et al. (2008) AlphaB-crystallin: a novel marker of invasive basal-like and metaplastic breast carcinomas. Annals of Diagnostic Pathology 12: 33-40.
14. Francis PJ, Berry V, Bhattacharya SS, Moore AT, (2000) The genetics of childhood cataract. J Med Genet 37: 481-488.
15. Bateman BJ, Harley RD, (1998) Genetics of eye disease; In: Nelson LB, editors. Philadelphia W.B. Saunders pp. 1-59.
16. Shiels A, Hejtmancik JF, (2007) Genetic origins of cataract. Arch Ophthalmol 125: 165-173.
17. Moore AT, (2004) Understanding the molecular genetics of congenital cataract may have wider implications for age related cataract. Br J Ophthalmol 88: 2-3.
18. Graw J, (2004) Congenital hereditary cataracts. Int J Dev Biol 48: 1031-1044.
19. Andley UP, (2006) Crystallins and hereditary cataracts: molecular mechanisms and potential for therapy. Expert Rev Mol Med 8: 1-19.
20. Litt M, Kramer P, LaMorticella DM, Murphey W, Lovrien EW, et al. (1998) Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Hum Mol Genet 7: 471-474.
21. Kmoch S, Brynda J, Asfaw B, Bezouska K, Novak P, et al. (2000) Link between a novel human gammaD-crystallin allele and a unique cataract phenotype explained by protein crystallography. Hum Mol Genet 9: 1779-1786.
22. Selcen D, Engel AG, (2003) Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. Annals of Neurology 54: 804-810.
23. Inagaki N, Hayashi T, Arimura T, Koga Y, Takahashi M, et al. (2006) Alpha B-crystallin mutation in dilated cardiomyopathy. Biochemical and Biophysical Research Communications 342: 379-386.
24. Liu Y, Zhang X, Luo L, Wu M, Zeng R, et al. (2006) A Novel {alpha}B-Crystallin Mutation Associated with Autosomal Dominant Congenital Lamellar Cataract. Invest Ophthalmol Vis Sci 47: 1069-1075.
25. Liu M, Ke T, Wang Z, Yang Q, Chang W, et al. (2006) Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family. Investigative Ophthalmology and Visual Science 47: 3461-3466.
26. Berry V, Francis P, Reddy MA, Collyer D, Vithana E, et al. (2001) Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. Am J Hum Genet 69: 1141-1145.
27. Bova MP, Yaron O, Huang Q, Ding L, Haley DA, et al. (1999) Mutation R120G in alphaB-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function. Proc Natl Acad Sci U S A 96: 6137-6142.
28. Perng MD, Wen SF, van den IP, Prescott AR, Quinlan RA, (2004) Desmin aggregate formation by R120G alphaB-crystallin is caused by altered filament interactions and is dependent upon network status in cells. Mol Biol Cell 15: 2335-2346.
29. Simon S, Michiel M, Skouri-Panet F, Lechaire JP, Vicart P, et al. (2007) Residue R120 is essential for the quaternary structure and functional integrity of human alphaB-crystallin. Biochemistry 46: 9605-9614.
30. Meehan S, Knowles TP, Baldwin AJ, Smith JF, Squires AM, et al. (2007) Characterisation of amyloid fibril formation by small heat-shock chaperone proteins human alphaA-, alphaB- and R120G alphaB-crystallins. J Mol Biol 372: 470-484.
31. Perng MD, Muchowski PJ, van Den IP, Wu GJ, Hutcheson AM, et al. (1999) The cardiomyopathy and lens cataract mutation in alphaB-crystallin alters its protein structure, chaperone activity, and interaction with intermediate filaments in vitro. J Biol Chem 274: 33235-33243.
32. Maloyan A, Sanbe A, Osinska H, Westfall M, Robinson D, et al. (2005) Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-B-crystallin desmin-related cardiomyopathy. Circulation 112: 3451-3461.
33. Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP, et al. (2007) Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130: 427-439.
34. Treweek TM, Rekas A, Lindner RA, Walker MJ, Aquilina JA, et al. (2005) R120G alphaB-crystallin promotes the unfolding of reduced alpha-lactalbumin and is inherently unstable. Febs J 272: 711-724.
35. den Engelsman J, Keijsers V, de Jong WW, Boelens WC, (2003) The small heat-shock protein alpha B-crystallin promotes FBX4-dependent ubiquitination. J Biol Chem 278: 4699-4704.
36. Sanbe A, Osinska H, Villa C, Gulick J, Klevitsky R, et al. (2005) Reversal of amyloid-induced heart disease in desmin-related cardiomyopathy. Proc Natl Acad Sci U S A 102: 13592-13597.
37. Kamradt MC, Chen F, Sam S, Cryns VL, (2002) The small heat shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation. J Biol Chem 277: 38731-38736.
38. Kamradt MC, Chen F, Cryns VL, (2001) The small heat shock protein alpha B-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. J Biol Chem 276: 16059-16063.
39. Li DW, Liu JP, Mao YW, Xiang H, Wang J, et al. (2005) Calcium-activated RAF/MEK/ERK signaling pathway mediates p53-dependent apoptosis and is abrogated by alpha B-crystallin through inhibition of RAS activation. Mol Biol Cell 16: 4437-4453.
40. Xi JH, Bai F, Gross J, Townsend RR, Menko AS, et al. (2008) Mechanism of small heat shock protein function in vivo: a knock-in mouse model demonstrates that the R49C mutation in alpha A-crystallin enhances protein insolubility and cell death. J Biol Chem 283: 5801-5814.
41. Skvorak K, Vissel B, Homanics GE, (2006) Production of conditional point mutant knockin mice. Genesis 44: 345-353.
42. White TW, (2002) Unique and redundant connexin contributions to lens development. Science 295: 319-320.
43. Andley UP, Hamilton PD, Ravi N, (2008) Mechanism of insolubilization by a single-point mutation in alphaA-crystallin linked with hereditary human cataracts. Biochemistry 47: 9697-9706.
44. Andley UP, (2009) AlphaA-crystallin R49Cneo mutation influences the architecture of lens fiber cell membranes and causes posterior and nuclear cataracts in mice. BMC Ophthalmol 9: 4.
45. Pietrowski D, Durante MJ, Liebstein A, Schmitt-John T, Werner T, et al. (1994) Alpha-crystallins are involved in specific interactions with the murine gamma D/E/F-crystallin-encoding gene. Gene 144: 171-178.
46. Song S, Hanson MJ, Liu BF, Chylack LT, Liang JJ, (2008) Protein-protein interactions between lens vimentin and alphaB-crystallin using FRET acceptor photobleaching. Mol Vis 14: 1282-1287.
47. Sandilands A, Wang X, Hutcheson AM, James J, Prescott AR, et al. (2004) Bfsp2 mutation found in mouse 129 strains causes the loss of CP49' and induces vimentin-dependent changes in the lens fibre cell cytoskeleton. Exp Eye Res 78: 875-889.
48. Richter L, Flodman P, Barria von-Bischhoffshausen F, Burch D, Brown S, et al. (2008) Clinical variability of autosomal dominant cataract, microcornea and corneal opacity and novel mutation in the alpha A crystallin gene (CRYAA). Am J Med Genet A 146: 833-842.
49. Vanita V, Singh JR, Hejtmancik JF, Nuernberg P, Hennies HC, et al. (2006) A novel fan-shaped cataract-microcornea syndrome caused by a mutation of CRYAA in an Indian family. Mol Vis 12: 518-522.
50. Andley UP, Reilly MA, (2010) In vivo lens deficiency of the R49C alphaA-crystallin mutant. Exp Eye Res 90: 699-702.
51. Goldfarb LG, Dalakas MC, (2009) Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease. Journal of Clinical Investigation 119: 1806-1813.
52. Schroder R, Schoser B, (2009) Myofibrillar myopathies: a clinical and myopathological guide. Brain Pathology 19: 483-492.
53. Head MW, Hurwitz L, Kegel K, Goldman JE, (2000) AlphaB-crystallin regulates intermediate filament organization in situ. Neuroreport 11: 361-365.
54. Ghosh JG, Houck SA, Clark JI, (2007) Interactive sequences in the stress protein and molecular chaperone human alphaB crystallin recognize and modulate the assembly of filaments. International Journal of Biochemistry and Cell Biology 39: 1804-1815.
55. Chavez Zobel AT, Loranger A, Marceau N, Theriault JR, Lambert H, et al. (2003) Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alphaB-crystallin mutant. Hum Mol Genet 12: 1609-1620.
56. Wang X, Osinska H, Klevitsky R, Gerdes AM, Nieman M, et al. (2001) Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circulation Research 89: 84-91.
57. Arrigo AP, Simon S, Gibert B, Kretz-Remy C, Nivon M, et al. (2007) Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Lett 581: 3665-3674.
58. Andley UP, Patel HC, Xi JH, (2002) The R116C mutation in alpha A-crystallin diminishes its protective ability against stress-induced lens epithelial cell apoptosis. J Biol Chem 277: 10178-10186.
59. Watson GW, Andley UP, (2010) Activation of the unfolded protein response by a cataract-associated alphaA-crystallin mutation. Biochemical and Biophysical Research Communications 401: 192-196.
60. Weihl CC, Miller SE, Hanson PI, Pestronk A, (2007) Transgenic expression of inclusion body myopathy associated mutant p97/VCP causes weakness and ubiquitinated protein inclusions in mice. Human Molecular Genetics 16: 919-928.