Loss of Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Leads to Photoreceptor Degeneration in rd11 Mice

Abstract

Purpose: : To characterize mouse lines with retinopathy as a critical means to uncover genes and pathways important for retinal biology and function.

Methods: : The rd11 strain of mice was identified at The Jackson Laboratory in a screen for retinal degeneration. An allelic strain, B6-JR2845, was subsequently characterized. We performed linkage analysis, positional cloning and a mutation screen to elucidate the gene responsible for the degeneration phenotype.

Results: : The lysophosphatidylcholine acyltransferase encoding gene, Lpcat1, was mutated in both strains. A 1 base pair insertion (c.420-421insG) in exon 3 and a 7 base pair deletion (c.14-20delGCCGCGG) in exon 1 were observed in rd11 and B6-JR2845 mice respectively. Both changes are expected to result in frameshift and premature truncation of the predicted protein. LPCAT1 has been previously shown to facilitate the conversion of pamitoyl-lysophosphatidylcholine to dipalmitoylphosphatidylcholine (DPPC) and has been suggested to be important for the production of lung surfactant. Retinal lipid extracts from rd11 and B6-JR2845 mice were determined to have substantially reduced DPPC when compared to C57Bl6 control.

Conclusions: : Our results suggest that the loss of LPCAT1 has a detrimental effect on the biology and lipid composition in the mouse retina. The result in the mouse is a rapid retinal degeneration.

Keywords: retinal degenerations: hereditary • gene screening • lipids