RGD Reference Report - A spontaneous mutation affects programmed cell death during development of the rat eye. - Rat Genome Database

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A spontaneous mutation affects programmed cell death during development of the rat eye.

Authors: Sinha, Debasish  Hose, Stacey  Zhang, Cheng  Neal, Rachel  Ghosh, Madhumita  O'Brien, Terrence P  Sundin, Olof  Goldberg, Morton F  Robison, W Gerald  Russell, Paul  Lo, Woo-Kuen  Samuel Zigler, J 
Citation: Sinha D, etal., Exp Eye Res. 2005 Mar;80(3):323-35. doi: 10.1016/j.exer.2004.09.014.
RGD ID: 126925760
Pubmed: PMID:15721615   (View Abstract at PubMed)
DOI: DOI:10.1016/j.exer.2004.09.014   (Journal Full-text)

We have discovered a spontaneous mutation in the Sprague-Dawley rat with a novel eye phenotype that we have named Nuc1. The Nuc1 mutation behaves as a single semi-dominant locus with an intermediate phenotype in the heterozygotes. Heterozygotes exhibit nuclear cataracts. Homozygous Nuc1 rats are fully viable and have microphthalmia, retinal abnormalities and disruption of lens structure shortly before birth. The homozygous mutant shows no obvious pathology outside of the eye, indicating that the mutation is highly eye specific in its effects. An unusual feature of the mutation is that it prevents the normal programmed loss of nuclei from lens fiber cells, but does not affect the loss of other organelles. TUNEL, light, and electron microscopic studies show normal intact nuclei in lens fibers, in contrast to many other models with degenerate nuclei and unlike normal lenses where no such nuclei remain. The beaded filament protein, filensin, is down-regulated in fibers of Nuc1, while heat shock cognate 70 is up-regulated. Homozygous retinas are thicker than normal, and TUNEL labeling indicates roughly half the number of apoptotic cells compared to a wild-type retina. The transient layer of Chievitz persists in adult Nuc1 retina, indicative of delayed development. Hence, Nuc1 is a novel mutation that could be an eye-specific regulator of apoptosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Cryba1  (crystallin, beta A1)
Cryba1Nuc1Dbsa  (crystallin, beta A1;Nuc1 mutant, Dbsa)

Genes (Mus musculus)
Cryba1  (crystallin, beta A1)

Genes (Homo sapiens)
CRYBA1  (crystallin beta A1)

SD-Cryba1Nuc1Dbsa  (NA)

Additional Information