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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Fine localization of a new cataract locus, Kec, on mouse chromosome 14 and exclusion of candidate genes as the gene that causes cataract in the Kec mouse

  • Published : 2008.09.30
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Abstract

A mouse with cataract, Kec, was generated from N-ethyl-N-nitrosourea (ENU) mutagenesis. Cataract in the Kec mouse was observable at about 5 weeks after birth and this gradually progressed to become completely opaque by 12 weeks. Dissection microscopy revealed that vacuoles with a radial or irregular shape were located primarily in the cortex of the posterior and equatorial regions of the lens. At the late stage, the lens structure was distorted, but not ruptured. This cataract phenotype was inherited in an autosomal recessive manner. We performed a genetic linkage analysis using 133 mutant and 67 normal mice produced by mating Kec mutant (BALB/c) and F1 (C57BL/6 $\times$ Kec) mice. The Kec locus was mapped to the 3 cM region encompassed by D14Mit34 and D14Mit69. In addition we excluded coding sequences of 9 genes including Rcbtb2, P2ry5, Itm2b, Med4, Nudt15, Esd, Lcp1, Slc25a30, and 2810032E02Rik as the candidate gene that causes cataract in the Kec mouse.

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References

  1. Hansen, L., Yao, W., Eiberg, H., Funding, M., Riise, R., Kjaer, K. W., Hejtmancik, J. F. and Rosenberg, T. (2006) The congenital "ant-egg" cataract phenotype is caused by a missense mutation in connexin46. Mol. Vis. 12, 1033-1039
  2. Grow, J. (2004) Congenital hereditary cataracts. Int. J. Dev. Biol. 48, 1031-1044 https://doi.org/10.1387/ijdb.041854jg
  3. Mackay, D., Ionides, A., Kibar, Z., Rouleau, G., Berry, V., Moore, A., Shiles, A. and Bhattacharya, S. (1999) Connexin46 mutations in autosomal dominant congenital cataract. Am. J. Hum. Genet. 64, 1357-1364 https://doi.org/10.1086/302383
  4. Messina-Baas, O. M. Gonzalez-Huerta, L. M. and Cuevas- Covarrubias, S. A. (2006) Two affected siblings with nuclear cataract associated with a novel missense mutation in the CRYGD gene. Mol. Vis. 12, 995-1000
  5. Brown, N. P. and Bron, A. J. (1996) Lens Disorders. Oxford, Butterworth, Heinemann Ltd
  6. Chang, B., Wang, X., Hawes, N. L., Ojakian, R., Davisson, M. T., Lo, W. K. and Gong, X. (2002) A Gja8 (Cx50) point mutation causes an alteration of ${\alpha}3$ connexin (Cx46) in semi-dominant cataracts of Lop 10 mice. Hum. Mol. Genet. 11, 507-513 https://doi.org/10.1093/hmg/11.5.507
  7. Francis, P. J., Berry, V., Moore, A. T. and Bhattacharya, S. (1999) Lens biology: development and human cataractogenesis. Trends Genet. 15, 191-196 https://doi.org/10.1016/S0168-9525(99)01738-2
  8. Graw, J. (1999) Mouse models of congenital cataract. Eye. 13, 438-444 https://doi.org/10.1038/eye.1999.118
  9. Grow, J. and Loster, J. (2003) Developmental genetics in ophthalmology. Ophthalmic Genet. 24, 1-33 https://doi.org/10.1076/opge.24.1.1.13888
  10. Justice, M. J., Noveroske, J. K., Weber, J. S., Zheng, B. and Bradley A. (1999) Mouse ENU mutagenesis. Hum. Mol. Genet. 8, 1955-1963 https://doi.org/10.1093/hmg/8.10.1955
  11. Russell, W. L., Kelly, E. M., Hunsicker, P. R., Bangham, J. W., Maddux, S. C. and Phipps, E. L. (1979) Specificlocus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc. Natl. Acad. Sci. U.S.A. 76, 5818-5819
  12. Cho, J., Cho, K., Yoon, S. and Song, C. (2004) Establishment of hereditary mouse with opaque and small eye by ENU mutagenesis. Korean J. Lab. An. Sci. 20, 300-304
  13. Smith, R. S., Sundberg, J. P. and Linder, C. C. (1997) Mouse Mutations as Models for Studying Cataracts. Pathobiology 65, 146-154 https://doi.org/10.1159/000164116
  14. Spencer, W. H. (1985) Ophthalmic Pathology. An Atlas and Textbook. Philadelphia, Saunders, vol 1, pp. 151-161, 423-479, vol 3, pp. 1396
  15. Harbor, B. (1997) Mouse Genome Database (MGD) Mouse Genome Informatics. The Jackson Laboratory, World Wide Web, URL:http://www.informatics.jax.org/
  16. Davisson, M. T., Lalley, P. A., Peters, J., Doolittle, D. P., Hillyard, A. L. and Searle, A. G. (1991) Report of the Comparative Subcommitte for Human, Mouse, and Other Rodents (HGM11). Cytogenet. Cell Gent. 58, 1152-1159 https://doi.org/10.1159/000133726
  17. Ionides, A., Francis, P., Berry, V., Mackay, D., Bhattacharya, S., Shiels, A. and Moore, A. (1999) Clinical and genetic heterogeneity in autosomal dominant cataract. Br. J. Ophthalmol. 83, 802-808 https://doi.org/10.1136/bjo.83.7.802
  18. Ren, Z., Li, A., Shastry, B. S., Padma, T., Ayyagari, R., Scott, M. H., Pasrks, M.M., Kaiser-Kupfer, M. I. and Hejtmancik, J. F. (2000) A 5-base insertion in the gammaC-crystallin gene is associated with autosomal dominant variable zonular pulverulent cataract. Hum. Genet. 106, 531-537 https://doi.org/10.1007/s004390050021
  19. Berry, V., Mackay, D., Khaliq, S., Francis, P. J., Hameed, A., Anwar, K., Mehdi, S. Q., Newbold, R. J., Ionides, A., Shiels, A., Moore, T. and Bhattacharya, S.S. (1999) Connexin50 mutation in a family with congenital "zonular nuclear" pulverulent cataract of Pakistani origin. Hum. Genet. 105, 168-170 https://doi.org/10.1007/s004390051082
  20. Polyakov, A. V., Shagina, L. A., Khlebnikova, O. V. and Evgrafov, O. V. (2001) Mutation in the connexin50 gene (GJA8) in a Russian family with zonular pulverulent cataract. Clin. Genet. 60, 476-478 https://doi.org/10.1034/j.1399-0004.2001.600614.x
  21. Shiels, A., Mackay, D., Ionides, A., Berry, V., Moore, A. and Bhattacharya, S. (1998) A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q. Am. J. Hum. Genet. 62, 526-532 https://doi.org/10.1086/301762
  22. Liu, M., Ke ,T., Wang, Z., Yang , Q., Cbang, W., Jiang, F., Tang, Z., Li, H., Ren, X., Wang, X., Wang, T., Li, Q., Yang, J., Liu, J. and Wang, K. (2006) Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family. IOVS 47, 3461-3466 https://doi.org/10.1167/iovs.05-1438
  23. Nam, Y., Kim, J., Cha, D., Cho, J., Cho, K., Yoon, S., Yoon, J., Oh, Y., Suh, J., Han, S., Song, C. and Yoon, S. (2006) A novel missense mutation in the mouse hairless gene causes irreversible hair loss: genetic and molecular analyses of Hr m1Enu. Genomics 87, 520-526 https://doi.org/10.1016/j.ygeno.2005.12.005
  24. Boyd, Y. (1998) Genetic Mapping of the Mouse Genome. Methods. 14, 120-34 https://doi.org/10.1006/meth.1997.0572
  25. Shin, H. D., Cheong, H. S., Park, B. L., Kim, L. H., Chang, S. H., Lee, I. H. and Park, S. K. (2008) Common MCL1 Polymorphisms associated with risk of tuberculosis. BMB Reports 41, 334-337 https://doi.org/10.5483/BMBRep.2008.41.4.334

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