N-ethyl-N-nitrosourea (ENU) induced mutations within the Klotho gene lead to ectopic calcification and reduced lifespan in mouse models

PLoS ONE

Volumn 10, Issue 4, 2015, Pages

  Esapa, Christopher T ^a,b   Hannan, Fadil M ^a,c   Babinsky, Valerie N ^a   Potter, Paul ^b   Thomas, Gethin P ^d   Croucher, Peter I ^e   Brown, Matthew A ^d   Brown, Steve D M ^b   Cox, Roger D ^b   Thakker, Rajesh V ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b MEDICAL RESEARCH COUNCIL   (United Kingdom)

^c UNIVERSITY OF LIVERPOOL   (United Kingdom)

^d UNIVERSITY OF QUEENSLAND   (Australia)

^e GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CALCITRIOL; ETHYLNITROSOUREA; FIBROBLAST GROWTH FACTOR 23; KLOTHO PROTEIN; PHOSPHATE; 1,25-DIHYDROXYVITAMIN D; BETA GLUCURONIDASE; FIBROBLAST GROWTH FACTOR; N ACETYLGALACTOSAMINYLTRANSFERASE; POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; STOP CODON; VITAMIN D;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTERY CALCIFICATION; ARTICLE; CALCIFICATION; CHROMOSOME 5; CONTROLLED STUDY; COS 7 CELL LINE; DNA SEQUENCE; ECALC1 GENE; ECALC2 GENE; ENDOPLASMIC RETICULUM; FEMALE; GENE; GENE EXPRESSION; GENE MAPPING; GENE MUTATION; IN VITRO STUDY; KIDNEY CALCIFICATION; KLOTHO GENE; LUNG CALCIFICATION; MALE; MISSENSE MUTATION; MOUSE; MOUSE MODEL; NONHUMAN; NONSENSE MUTATION; PHOSPHATE BLOOD LEVEL; PHOSPHATE METABOLISM; PREMATURE AGING; PROTEIN STABILITY; TUMOR CALCINOSIS; ALLELE; AMINO ACID SEQUENCE; ANALOGS AND DERIVATIVES; ANIMAL; BLOOD; C57BL MOUSE; CALCINOSIS; CHEMISTRY; CHLOROCEBUS AETHIOPS; COS CELL LINE; DISEASE MODEL; DRUG EFFECTS; GENE LOCUS; GENETICS; GENOTYPE; HUMAN; KIDNEY; LONGEVITY; METABOLISM; MOLECULAR GENETICS; PATHOLOGY; PHENOTYPE; SEQUENCE ALIGNMENT; SINGLE NUCLEOTIDE POLYMORPHISM; STOP CODON;

MUS;

ALLELES; AMINO ACID SEQUENCE; ANIMALS; CALCINOSIS; CERCOPITHECUS AETHIOPS; CODON, NONSENSE; COS CELLS; DISEASE MODELS, ANIMAL; ENDOPLASMIC RETICULUM; ETHYLNITROSOUREA; FIBROBLAST GROWTH FACTORS; GENETIC LOCI; GENOTYPE; GLUCURONIDASE; HUMANS; KIDNEY; LONGEVITY; MALE; MICE; MICE, INBRED C57BL; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; N-ACETYLGALACTOSAMINYLTRANSFERASES; PHENOTYPE; PHOSPHATES; POLYMORPHISM, SINGLE NUCLEOTIDE; SEQUENCE ALIGNMENT; VITAMIN D;

EID: 84928911807     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0122650     Document Type: Article

References (51)

1. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003; 18:1731-1740. PMID: 12937218
2. Whyte MP (2006) Extraskeletal (Ectopic) Calcification and Ossification. Primer on the metabolic bone diseases and disorders of mineral metabolism: 436-437. Editor: Favus MJ. Publisher: The American Society for Bone and Mineral Research.
3. Wu M, Rementer C, Giachelli CM. Vascular calcification: an update on mechanisms and challenges in treatment. Calcif Tissue Int. 2013; 93:365-373. doi: 10.1007/s00223-013-9712-z PMID: 23456027
4. Rutsch F, Ruf N, Vaingankar S, Toliat MR, Suk A, Hohne W, et al. Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification. Nat Genet. 2003; 34:379-381. PMID: 12881724
5. Pendleton A, Johnson MD, Hughes A, Gurley KA, Ho AM, Doherty M, et al. Mutations in ANKH cause chondrocalcinosis. Am J Hum Genet. 2002; 71:933-940. PMID: 12297987
6. Farrow EG, Imel EA, White KE. Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and alphaKlotho). Best Pract Res Clin Rheumatol. 2011; 25:735-747. doi: 10.1016/j.berh.2011.10.020 PMID: 22142751
7. Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev. 2012; 92:131-155. doi: 10.1152/physrev.00002.2011 PMID: 22298654
8. Benet-Pages A, Orlik P, Strom TM, Lorenz-Depiereux B. An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia. Hum Mol Genet. 2005; 14:385-390. PMID: 15590700
9. Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, et al. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest. 2007; 117:2684-2691. PMID: 17710231
10. Ichikawa S, Sorenson AH, Austin AM, Mackenzie DS, Fritz TA, Moh A, et al. Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression. Endocrinology. 2009; 150:2543-2550. doi: 10.1210/en.2008-0877 PMID: 19213845
11. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997; 390:45-51. PMID: 9363890
12. Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest. 2004; 113:561-568. PMID: 14966565
13. Topaz O, Shurman DL, Bergman R, Indelman M, Ratajczak P, Mizrachi M, et al. Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet. 2004; 36:579-581. PMID: 15133511
14. Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998; 242:626-630. PMID: 9464267
15. Mian IS. Sequence, structural, functional, and phylogenetic analyses of three glycosidase families. Blood Cells Mol Dis. 1998; 24:83-100. PMID: 9779294
16. Tohyama O, Imura A, Iwano A, Freund JN, Henrissat B, Fujimori T, et al. Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides. J Biol Chem. 2004; 279:9777-9784. PMID: 14701853
17. Goetz R, Nakada Y, Hu MC, Kurosu H, Wang L, Nakatani T, et al. Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proc Natl Acad Sci U S A. 2010; 107:407-412. doi: 10.1073/pnas.0902006107 PMID: 19966287
18. Acevedo-Arozena A, Wells S, Potter P, Kelly M, Cox RD, Brown SD. ENU mutagenesis, a way forward to understand gene function. Annu Rev Genomics Hum Genet. 2008; 9:49-69. PMID: 18949851
19. Bentley L, Esapa CT, Nesbit MA, Head RA, Evans H, Lath D, et al. An N-ethyl-N-nitrosourea induced corticotropin-releasing hormone promoter mutation provides a mouse model for endogenous glucocorticoid excess. Endocrinology. 2014; 155:908-922. doi: 10.1210/en.2013-1247 PMID: 24302625
20. Esapa CT, Head RA, Jeyabalan J, Evans H, Hough TA, Cheeseman MT, et al. A mouse with an N-Ethyl-N-nitrosourea (ENU) Induced Trp589Arg Galnt3 mutation represents a model for hyperphosphataemic familial tumoural calcinosis. PLoS One. 2012; 7:e43205. doi: 10.1371/journal.pone.0043205 PMID: 22912827
21. Piret SE, Esapa CT, Gorvin CM, Head R, Loh NY, Devuyst O, et al. A mouse model of early-onset renal failure due to a xanthine dehydrogenase nonsense mutation. PLoS One. 2012; 7:e45217. PMID: 23024809
22. Lindberg K, Amin R, Moe OW, Hu MC, Erben RG, Ostman Wernerson A, et al. The Kidney Is the Principal Organ Mediating Klotho Effects. J Am Soc Nephrol. 2014.
23. Hardisty-Hughes RE, Parker A, Brown SD. A hearing and vestibular phenotyping pipeline to identify mouse mutants with hearing impairment. Nat Protoc. 2010; 5:177-190. doi: 10.1038/nprot.2009.204 PMID: 20057387
24. Nolan PM, Peters J, Strivens M, Rogers D, Hagan J, Spurr N, et al. A systematic, genome-wide, pheno-type- driven mutagenesis programme for gene function studies in the mouse. Nat Genet. 2000; 25: 440-443. PMID: 10932191
25. Stechman MJ, Ahmad BN, Loh NY, Reed AA, Stewart M, Wells S, et al. Establishing normal plasma and 24-hour urinary biochemistry ranges in C3H, BALB/c and C57BL/6J mice following acclimatization in metabolic cages. Lab Anim. 2010; 44:218-225. doi: 10.1258/la.2010.009128 PMID: 20457824
26. Hannan FM, Nesbit MA, Christie PT, Fratter C, Dudley NE, Sadler GP, et al. Familial isolated primary hyperparathyroidism caused by mutations of the MEN1 gene. Nat Clin Pract Endocrinol Metab. 2008; 4:53-58. PMID: 18084346
27. Nesbit MA, Bowl MR, Harding B, Ali A, Ayala A, Crowe C, et al. Characterization of GATA3 mutations in the hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome. J Biol Chem. 2004; 279:22624-22634. PMID: 14985365
28. Williams SE, Reed AA, Galvanovskis J, Antignac C, Goodship T, Karet FE, et al. Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum. Hum Mol Genet. 2009; 18:2963-2974. doi: 10.1093/hmg/ddp235 PMID: 19465746
29. Arking DE, Krebsova A, Macek M Sr., Macek M Jr., Arking A, Mian IS, et al. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A. 2002; 99:856-861. PMID: 11792841
30. Kroger H, Vainio P, Nieminen J, Kotaniemi A. Comparison of different models for interpreting bone mineral density measurements using DXA and MRI technology. Bone. 1995; 17:157-159. PMID: 8554924
31. Quwailid MM, Hugill A, Dear N, Vizor L, Wells S, Horner E, et al. A gene-driven ENU-based approach to generating an allelic series in any gene. Mamm Genome. 2004; 15:585-591. PMID: 15457338
32. Keays DA, Clark TG, Flint J. Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens. Mamm Genome. 2006; 17:230-238. PMID: 16518690
33. Carpinelli MR, Wise AK, Burt RA. Vitamin D-deficient diet rescues hearing loss in Klotho mice. Hear Res. 2011; 275:105-109. doi: 10.1016/j.heares.2010.12.009 PMID: 21167925
34. Ohnishi M, Nakatani T, Lanske B, Razzaque MS. Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase. Kidney Int. 2009; 75:1166-1172. doi: 10.1038/ki.2009.24 PMID: 19225558
35. Kawaguchi H, Manabe N, Miyaura C, Chikuda H, Nakamura K, Kuro-o M. Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. J Clin Invest. 1999; 104:229-237. PMID: 10430604
36. Yamashita T, Nabeshima Y, Noda M. High-resolution micro-computed tomography analyses of the abnormal trabecular bone structures in klotho gene mutant mice. J Endocrinol. 2000; 164:239-245. PMID: 10657859
37. Yuan Q, Sato T, Densmore M, Saito H, Schuler C, Erben RG, et al. Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice. PLoS Genet. 2012; 8:e1002726. doi: 10.1371/journal.pgen.1002726 PMID: 22615584
38. Kim HJ, Delaney JD, Kirsch T. The role of pyrophosphate/phosphate homeostasis in terminal differentiation and apoptosis of growth plate chondrocytes. Bone. 2010; 47:657-665. doi: 10.1016/j.bone.2010.06.018 PMID: 20601283
39. Lysaght AC, Yuan Q, Fan Y, Kalwani N, Caruso P, Cunnane M, et al. FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice. PLoS One. 2014; 9:e107681. doi: 10.1371/journal.pone.0107681 PMID: 25243481
40. Ichikawa S, Baujat G, Seyahi A, Garoufali AG, Imel EA, Padgett LR, et al. Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations. Am J Med Genet A. 2010; 152A:896-903. doi: 10.1002/ajmg.a.33337 PMID: 20358599
41. Ford-Hutchinson AF, Cooper DM, Hallgrimsson B, Jirik FR. Imaging skeletal pathology in mutant mice by microcomputed tomography. J Rheumatol. 2003; 30:2659-2665. PMID: 14719210
42. Li Q, Guo H, Chou DW, Berndt A, Sundberg JP, Uitto J. Mutant Enpp1asj mice as a model for generalized arterial calcification of infancy. Dis Model Mech. 2013; 6:1227-1235. doi: 10.1242/dmm.012765 PMID: 23798568
43. Yoshida T, Fujimori T, Nabeshima Y. Mediation of unusually high concentrations of 1,25-dihydroxyvitamin D in homozygous klotho mutant mice by increased expression of renal 1alpha-hydroxylase gene. Endocrinology. 2002; 143:683-689. PMID: 11796525
44. Utsugi T, Ohno T, Ohyama Y, Uchiyama T, Saito Y, Matsumura Y, et al. Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging. Metabolism. 2000; 49:1118-1123. PMID: 11016890
45. Razzaque MS. The role of Klotho in energy metabolism. Nat Rev Endocrinol. 2012; 8:579-587. doi: 10.1038/nrendo.2012.75 PMID: 22641000
46. Suga T, Kurabayashi M, Sando Y, Ohyama Y, Maeno T, Maeno Y, et al. Disruption of the klotho gene causes pulmonary emphysema in mice. Defect in maintenance of pulmonary integrity during postnatal life. Am J Respir Cell Mol Biol. 2000; 22:26-33. PMID: 10615062
47. Morishita K, Shirai A, Kubota M, Katakura Y, Nabeshima Y, Takeshige K, et al. The progression of aging in klotho mutant mice can be modified by dietary phosphorus and zinc. J Nutr. 2001; 131: 3182-3188. PMID: 11739863
48. Tucker Zhou TB, King GD, Chen C, Abraham CR. Biochemical and functional characterization of the klotho-VS polymorphism implicated in aging and disease risk. J Biol Chem. 2013; 288:36302-36311. doi: 10.1074/jbc.M113.490052 PMID: 24217253
49. Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro OM, Huang CL. Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. Proc Natl Acad Sci U S A. 2008; 105:9805-9810. doi: 10.1073/pnas.0803223105 PMID: 18606998
50. Hayashi Y, Okino N, Kakuta Y, Shikanai T, Tani M, Narimatsu H, et al. Klotho-related protein is a novel cytosolic neutral beta-glycosylceramidase. J Biol Chem. 2007; 282:30889-30900. PMID: 17595169
51. Noguchi J, Hayashi Y, Baba Y, Okino N, Kimura M, Ito M, et al. Crystal structure of the covalent intermediate of human cytosolic beta-glucosidase. Biochem Biophys Res Commun. 2008; 374:549-552. doi: 10.1016/j.bbrc.2008.07.089 PMID: 18662675