A QTL on Chromosome 10 Modulates Cone Photoreceptor Number in the Mouse Retina

PURPOSE. This investigation examines the genetic sources of marked variation in cone photoreceptor number among inbred lines of mice, identifying candidate genes that may control the proliferation, differentiation, or survival of this neuronal population. METHODS. Cone photoreceptor populations were counted in C57BL/6J (B6/J) and A/J strains, and 26 recombinant inbred (RI) strains derived from them. Eyes from RI strains were also collected for microarray analysis. Quantitative trait locus (QTL) analysis was carried out by simple and composite interval mapping and validated using a consomic line. Candidate genes were evaluated based on genetic variance between the parental strains and analysis of gene expression. Expression data, deposited in GeneNetwork (www.GeneNetwork.org), were used to generate a coexpression network of established cone photoreceptor genes as a reference standard. RESULTS. B6/J has 70% more cone photoreceptors than A/J. A significant QTL was mapped to chromosome 10 (Chr 10) and confirmed using B6.A < 10 > mice. Of 19 positional candidate genes, one-the myeloblastosis oncogene (Myb)-stood out. Myb has a potentially damaging missense mutation, high retinal expression, and a known role in cell proliferation. The ectonucleotide pyrophosphatase/phosphodiesterase 1 gene (Enpp1) was a second strong candidate, with an expression pattern that covaried with cone photoreceptors and that was differentially expressed between the parental strains. Enpp1 and several other candidate genes covaried with multiple genes within the cone photoreceptor gene network. CONCLUSIONS. The mouse retina shows marked variation in cone photoreceptor number, some of which must be controlled by polymorphisms in a gene or genes on Chr 10. (Invest Ophthalmol Vis Sci. 2011;52:3228-3236) DOI:10.1167/iovs.10-6693