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.
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.
Authors: M Danciger; M T Matthes; D Yasamura; N B Akhmedov; T Rickabaugh; S Gentleman; T M Redmond; M M La Vail; D B Farber Journal: Mamm Genome Date: 2000-06 Impact factor: 2.957
Authors: Jonathan B Singer; Annie E Hill; Lindsay C Burrage; Keith R Olszens; Junghan Song; Monica Justice; William E O'Brien; David V Conti; John S Witte; Eric S Lander; Joseph H Nadeau Journal: Science Date: 2004-03-18 Impact factor: 47.728
Authors: Toco Y P Chui; Hongxin Song; Christopher A Clark; Joel A Papay; Stephen A Burns; Ann E Elsner Journal: Invest Ophthalmol Vis Sci Date: 2012-06-14 Impact factor: 4.799
Authors: Patrick W Keeley; Irene E Whitney; Nils R Madsen; Ace J St John; Sarra Borhanian; Stephanie A Leong; Robert W Williams; Benjamin E Reese Journal: Dev Cell Date: 2014-06-19 Impact factor: 12.270
Authors: Irene E Whitney; Mary A Raven; Daniel C Ciobanu; Ross A Poché; Qian Ding; Yasser Elshatory; Lin Gan; Robert W Williams; Benjamin E Reese Journal: Proc Natl Acad Sci U S A Date: 2011-05-16 Impact factor: 11.205
Authors: Jung-Woong Kim; Hyun-Jin Yang; Adam Phillip Oel; Matthew John Brooks; Li Jia; David Charles Plachetzki; Wei Li; William Ted Allison; Anand Swaroop Journal: Dev Cell Date: 2016-06-20 Impact factor: 12.270
Authors: Sammy C S Lee; Erin J Cowgill; Ali Al-Nabulsi; Emma J Quinn; Sylvia M Evans; Benjamin E Reese Journal: J Neurosci Date: 2011-10-05 Impact factor: 6.167
Authors: Irene E Whitney; Patrick W Keeley; Ace J St John; Amanda G Kautzman; Jeremy N Kay; Benjamin E Reese Journal: J Neurosci Date: 2014-07-23 Impact factor: 6.167