A mutation in the start codon of gamma-crystallin D leads to nuclear cataracts in the Dahl SS/Jr-Ctr strain

作者：Johnson Ashley C; Lee Jonathan W; Harmon Ashlyn C; Morris Zaliya; Wang Xuexiang; Fratkin Jonathan; Rapp John P; Gomez Sanchez Elise; Garrett Michael R^*

来源：Mammalian Genome, 2013, 24(3-4): 95-104.

DOI：10.1007/s00335-013-9447-1

Cataracts are a major cause of blindness. The most common forms of cataracts are age- and UV-related and develop mostly in the elderly, while congenital cataracts appear at birth or in early childhood. The Dahl salt-sensitive (SS/Jr) rat is an extensively used model of salt-sensitive hypertension that exhibits concomitant renal disease. In the mid-1980s, cataracts appeared in a few animals in the Dahl S colony, presumably the result of a spontaneous mutation. The mutation was fixed and bred to establish the SS/Jr-Ctr substrain. The SS/Jr-Ctr substrain has been used exclusively by a single investigator to study the role of steroids and hypertension. Using a classical positional cloning approach, we localized the cataract gene with high resolution to a less than 1-Mbp region on chromosome 9 using an F-1(SS/Jr-Ctr x SHR) x SHR backcross population. The 1-Mbp region contained only 13 genes, including 4 genes from the gamma-crystallins (Cryg) gene family, which are known to play a role in cataract formation. All of the gamma-crystallins were sequenced and a novel point mutation in the start codon (ATG -%26gt; GTG) of the Crygd gene was identified. This led to the complete absence of the CRYGD protein in the eyes of the SS/Jr-Ctr strain. In summary, the identification of the genetic cause in this novel cataract model may provide an opportunity to better understand the development of cataracts, particularly in the context of hypertension.

• 出版日期2013-4