This spontaneous mutation is valuable for the study of photoreceptor and retinal degeneration, particularly the role of specific fatty acids in this process, as well as other biological processes involving fatty acid regulation by Lpcat1.Read More +
In Lpcat1rd11 homozygotes photoreceptors develop normally, but degenerate quickly after 21 days of age, with less than half the normal number of rows of photoreceptor nuclei remaining by 31 days of age, and even fewer at 47 days of age. By 36 days of age retinal vessels are attenuated and by 113 days of age there is clear retinal degeneration. Dark-adapted electroretinography shows a reduced rod photoreceptor a-wave at 3 weeks of age, which is flattened by 4 weeks of age. Cone photoreceptor response is normal at 3 weeks of age but substantially reduced at 4 and 5 weeks of age. Lipid extracts from retina analyzed by HPLC and mass spectrometry show that the ratio of dipalmitoylphosphatidylcholine (DPPC) to the peak lipid class is decreased from 84% in C57BL/6J to 38% in Lpcat1rd11 homozygotes. Distinctly lower levels of platelet activating factor C16 and lyso-platelet activating factor C16 were found in retinas of homozygotes compared with C57BL/6J. Administration of DPPC in the chow did not prevent retinal degeneration. The Lpcat1rd11 allele seems slightly more severe than the Lpcat1rd11-2J allele.
|Allele Name||retinal degeneration 11|
|Gene Symbol and Name||Lpcat1, lysophosphatidylcholine acyltransferase 1|
|Strain of Origin||B6.D2/22Ei|
|General Note||Phenotypic Similarity to Human Syndrome: Retinal Degeneration J:229509 .|
|Molecular Note||This spontaneous insertion of a single G residue in exon 3 causes a frame shift predicted to encode an abnormal protein sequence after amino acid 140 and a stop codon after residue 178. RT-PCR of retinal RNA shows a 3 fold decrease in expression level and western blotting fails to detect protein product.|