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Mutation in the Ercc2 gene of the mouse causes cataracts
Author(s) -
Graw J.,
Kunze S.,
Dalke C.,
Fuchs H.,
Klaften M.,
Sabrautzki S.,
Hrabe de Angelis M.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0163
Subject(s) - cataracts , biology , ercc2 , genetics , mutation , mutant , dna repair , gene , nucleotide excision repair
Summary Cataracts have been associated with many mutations. In a large‐scale high‐throughput ENU mutagenesis screen we analyzed the offspring of paternally treated C3HeB/FeJ mice for obvious ocular dysmorphologies. We identified a mutant suffering from rough coat and small eyes only in homozygotes; homozygous females turned out to be sterile. The mutation was mapped to chromosome 7 between the markers 116J6.1 and D7Mit294 . The critical interval (8.6 Mb) contains 3 candidate genes ( Apoe , Six5 , Opa3 ); none of them showed a mutation. Using exome sequencing, we identified a c.2209T>C mutation in the Xpd / Ercc2 gene leading to a Ser737Pro exchange. During embryonic development, the mutant eyes did not show major changes. Postnatal histological analyses demonstrated small cortical vacuoles; later, cortical cataracts developed. Since XPD / ERCC 2 is involved in DNA repair, we checked also for the presence of the repair‐associated histone γ H2 AX in the lens. During the time, when primary lens fiber cell nuclei are degraded, γ H2 AX was strongly expressed in the cell nuclei; later, it demarcates clearly the border of the lens cortex to the organelle‐free zone. These findings demonstrate the importance of XPD / ERCC 2 for lens fiber cell differentiation.