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 Lpcat1rd11-2J 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 120 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 5 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 41% in rd11-2J 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 Lpcat1rd11-2J allele seems slightly less severe than the Lpcat1rd11 allele.
The retinal degeneration 11 2 Jackson mutation arose spontaneously in approximately 2002 at The Jackson Laboratory in the strain C.B-H2b Tg(H2-Dd)D8Gja/LilJ. This mutation was backcrossed onto C57BL/6J for 5 generations then intercrossed and bred to homozygosity, and during the backcrossing the transgene was bred out of this mutant subline.
|Allele Name||retinal degeneration 11 2 Jackson|
|Allele Synonym(s)||B6-JR2845; Nm3344|
|Gene Symbol and Name||Lpcat1, lysophosphatidylcholine acyltransferase 1|
|Strain of Origin||C.B-H2b Tg(H2-Dd)D8Gja/LilJ|
|Molecular Note||This is a spontaneous deletion of 7 nucleotodes in exon 1 in a GC rich region which is predicted to result in a frameshift after codon 8 and a stop codon after 21. RT-PCR of retinal RNA reveals a 2.5 fold increase in transcript, but western blotting failed to detect protein product.|