The nmf193 mutant was generated by a large-scale ENU mutagenesis screen and originally described as having a dominantly inherited phenotype characterized by fundus abnormalities. We determined that nmf193 mice exhibit outer-segment defects and progressive retinal degeneration. Clinical examination revealed retinal spotting apparent at 6 weeks of age. Histologic analysis of homozygous mutant mice at 6 weeks indicated an absence of outer segments (OS) and a 50% reduction of photoreceptor cells which progressed to complete loss of photoreceptors by 10 months. Mice heterozygous for the nmf193 mutation had a less severe phenotype of shortened outer segments at 2 months with progressive loss of photoreceptor cells to 50% by 10 months. A positional cloning approach using a DNA pooling strategy was performed to identify the causative mutation in nmf193 mice. The nmf193 mutation was linked to chromosome 17 and fine mapped to an interval containing the peripherin/rds (Prph2) gene. Mutation analysis identified a single base change in Prph2 that causes aberrant splicing between exons 1 and 2. Interestingly, a comparative histologic analysis demonstrated that Prph2 nmf193/+ mutants have similar photoreceptor degeneration to that of Nr2e3 rd7/rd7 . We show that Prph2 mRNA and protein levels are reduced in the Nr2e3 rd7/rd7 mutant compared to control littermates. Chromatin immunoprecipitation analysis shows that Prph2 is a direct target of NR2E3. In addition, the downregulation of Prph2 gene expression is similar in both the Nr2e3 rd7/rd7 and Prph2 nmf193/+ mutants, suggesting that the reduction of Prph2 may contribute to the degenerative pathology seen in Nr2e3 rd7/rd7 .
Mammalian Genome – Springer Journals
Published: Sep 3, 2008
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera