Cataracts, or lens opacities, are the leading cause of blindness worldwide. Cataracts are treatable with surgery, however, currently, no other therapies are available that could either inhibit, slow down, or reverse the development of cataracts. Therefore, it is necessary to expand our current knowledge of biological processes that lead to cataracts. The goals of this study are to develop mouse cataract models defined on molecular level that show how mutations in genes important for lens transparency correlate with functional, structural and biochemical abnormalities resulting in cataracts. ? This study focuses on two mouse cataract models of nuclear cataracts: coralliform cataract (Coc) is ? an autosomal dominant cataract that maps to 28.06 cM on mouse chromosome 16 in the region with synteny with HSA3q13-q21; lens opacity 4 (Lop4) is a semidominant nuclear cataract that maps to 96 cM on mouse chromosome 2 in the region of synteny with HSA20q11-q13.
The specific aims of this study are: ? Specific Aim (1): Fine linkage map Coc and Lop4 loci to reduce the critical regions to < 1Mb. ? Specific Aim (2): Establish BAC minimal tiling path over Coc and Lop4 critical regions. ? Specific Aim (3): Identify and test positional candidate genes for causal association with the disease. ? Specific Aim (4): Once genes and mutations responsible for the Coc and Lop4 phenotypes are identified, the focus will be on characterizing the process of cataract development at the molecular level. ? ? ?

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-AED (01))
Program Officer
Chin, Hemin R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Medical College of Wisconsin
Schools of Medicine
United States
Zip Code
Liegel, Ryan P; Ronchetti, Adam; Sidjanin, D J (2014) Alkylglycerone phosphate synthase (AGPS) deficient mice: models for rhizomelic chondrodysplasia punctate type 3 (RCDP3) malformation syndrome. Mol Genet Metab Rep 1:299-311
Liegel, R; Chang, B; Dubielzig, R et al. (2011) Blind sterile 2 (bs2), a hypomorphic mutation in Agps, results in cataracts and male sterility in mice. Mol Genet Metab 103:51-9
Merath, Kate M; Chang, Bo; Dubielzig, Richard et al. (2011) A spontaneous mutation in Srebf2 leads to cataracts and persistent skin wounds in the lens opacity 13 (lop13) mouse. Mamm Genome 22:661-73
Liang, Lina; Liegel, Ryan; Endres, Brad et al. (2011) Functional analysis of the Hsf4(lop11) allele responsible for cataracts in lop11 mice. Mol Vis 17:3062-71
Hassemer, E L; Le Gall, S M; Liegel, R et al. (2010) The waved with open eyelids (woe) locus is a hypomorphic mouse mutation in Adam17. Genetics 185:245-55
Talamas, Elijah; Jackson, Lavinia; Koeberl, Matthew et al. (2006) Early transposable element insertion in intron 9 of the Hsf4 gene results in autosomal recessive cataracts in lop11 and ldis1 mice. Genomics 88:44-51
Hunter, Linda S; Sidjanin, Duska J; Johnson, Jennifer L et al. (2006) Radiation hybrid mapping of cataract genes in the dog. Mol Vis 12:588-96
Sidjanin, D J; McElwee, J; Miller, B et al. (2005) Cloning of canine galactokinase (GALK1) and evaluation as a candidate gene for hereditary cataracts in Labrador retrievers. Anim Genet 36:265-6