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

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Abstract

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 F1(SS/Jr-Ctr × SHR) × SHR backcross population. The 1-Mbp region contained only 13 genes, including 4 genes from the γ-crystallins (Cryg) gene family, which are known to play a role in cataract formation. All of the γ-crystallins were sequenced and a novel point mutation in the start codon (ATG → 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.

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Acknowledgments

MRG is supported by NIH/NHLBI HL094446 and the Robert M. Hearin Foundation. ACH is supported by 1T32HL105324. EGS is supported by Medical Research funds from the Department of Veterans Affairs and NIH Grants HL27255 and HL75321.

Disclosures

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Ashley C. Johnson, Jonathan W. Lee, Ashlyn C. Harmon, Zaliya Morris, Xuexiang Wang, Elise Gomez-Sanchez & Michael R. Garrett

  2. Department of Medicine (Nephrology), University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Michael R. Garrett

  3. Department of Pathology, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Jonathan Fratkin

  4. G. V. (Sonny) Montgomery VAMC, Jackson, MS, 39216, USA

    Elise Gomez-Sanchez

  5. University of Toledo, College of Medicine, Toledo, OH, USA

    John P. Rapp

  6. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA

    Michael R. Garrett

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  1. Ashley C. Johnson
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  2. Jonathan W. Lee
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  3. Ashlyn C. Harmon
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Correspondence to Michael R. Garrett.

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Johnson, A.C., Lee, J.W., Harmon, A.C. et al. A mutation in the start codon of γ-crystallin D leads to nuclear cataracts in the Dahl SS/Jr-Ctr strain. Mamm Genome 24, 95–104 (2013). https://doi.org/10.1007/s00335-013-9447-1

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  • DOI: https://doi.org/10.1007/s00335-013-9447-1

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