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Splicing defect in Calpain12 cDNA of a recessive cataract mutation in rats (cat).

Vortrag: EVER - Annual Meeting, 30th September - 3rd October 2009, Portoroz, Slovenia. (2009)
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The recessive cataract mutation cat was identified among F2 offspring of Wistar rats having been treated with X irradiation; a corresponding mutant line was established (Léonard & Maisin, Nature 205, 1965, 615-6). To identify the underlying mutation, homozygous cat rats have been outcrossed to wild-type Brown Norway rats; heterozygous F1 offspring (without cataracts) have been backcrossed to parental homozygous cat rats. Among 461 F2 offspring, we observed in total 223 cataracts (48.5%) at the age of 10 weeks; however, 2/3 of these cataracts were discovered at the age of 3 weeks, and most of the remaining third at the age of 7-8 weeks. Linkage analysis located the mutation on rat chromosome 1 between the markers D1Got76 (76.2 MB) and D1Rat410 (87.6MB). This large interval contains candidate genes like Six5 and Opa3, which have been excluded by sequence analysis of cDNA from rat lenses. Recently, we identified a major splicing error in lens-derived cDNA of the gene Capn12 encoding Calpain-12. Besides exon 1, the transcript contains the complete intron 1; in exon 2 it keeps just a few bases to go to the end of intron 4 and than to exon 5; from there no further deviation from the wild-type sequence was yet observed. It is predicted that the sequence of the first intron leads to a premature stop codon after 10 new amino acids, which might result in a loss of Calpain-12 activity. Calpains has been proposed for a long time to be involved in cataractogenesis. Here we present for the first time a mutation in a calpain-encoding gene (Capn12), which is very likely to be responsible for cataract formation.
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Publikationstyp Sonstiges: Vortrag
Konferenztitel EVER - Annual Meeting
Konferzenzdatum 30th September - 3rd October 2009
Konferenzort Portoroz, Slovenia