An allele of microtubule-associated protein 1A (Mtap1a) reduces photoreceptor degeneration in Tulp1 and Tub Mutant Mice.

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Alleles, Animals, Disease Models, Animal, Eye Proteins, Mice, Mice, Inbred AKR, Microtubule-Associated Proteins, Photoreceptor Cells, Vertebrate, Polymorphism, Single Nucleotide, Proteins, Retinal Cone Photoreceptor Cells, Retinal Degeneration, Retinal Rod Photoreceptor Cells, Retinitis Pigmentosa

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Invest Ophthalmol Vis Sci 2012 Mar 26; 53(3):1663-9.




PURPOSE: To identify genes that modify photoreceptor cell loss in the retinas of homozygous Tulp1(tm1Pjn) and Tub(tub) mice, which exhibit juvenile retinitis pigmentosa.

METHODS: Modifier loci were identified by genetic quantitative trait locus analysis. F2 Tulp1(tm1Pjn/tm1Pjn) mutant mice from a B6-Tulp1(tm1Pjn/tm1Pjn) × AKR/J intercross were genotyped with a panel of single nucleotide polymorphism markers and phenotyped by histology for photoreceptor nuclei remaining at 9 weeks of age. Genotype and phenotype data were correlated and examined with Pseudomarker 2.02 using 128 imputations to map modifier loci. Thresholds for the 63%, 10%, 5%, and 1% significance levels were obtained from 100 permutations. A significant, protective candidate modifier was identified by bioinformatic analysis and confirmed by crossing transgenic mice bearing a protective allele of this gene with Tulp1- and Tub-deficient mice.

RESULTS: A significant, protective modifier locus on chromosome 2 and a suggestive locus on chromosome 13 that increases photoreceptor loss were identified in a B6-Tulp1(tm1Pjn/tm1Pjn) × AKR/J intercross. The chromosome 2 locus mapped near Mtap1a, which encodes a protein associated with microtubule-based intracellular transport and synapse function. The protective Mtap1a(129P2/OlaHsd) allele was shown to reduce photoreceptor loss in both Tulp1(tm1Pjn/tm1Pjn) and Tub(tub/tub) mice.

CONCLUSIONS: It was demonstrated that the gene Mtap1a, which modifies hearing loss in Tub(tub/tub) mice, also modifies retinal degeneration in Tub(tub/tub) and Tulp1(tm1Pjn/tm1Pjn) mice. These results suggest that functionally nonredundant members of the TULP family (TUB and TULP1) share a common functional interaction with MTAP1A.