An allele of microtubule-associated protein 1A (Mtap1a) reduces photoreceptor degeneration in Tulp1 and Tub Mutant Mice.
OBJECTIVE
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.
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Dennis M
DM
Maddox
Sakae
S
Ikeda
Akihiro
A
Ikeda
Weidong
W
Zhang
Mark P
MP
Krebs
Patsy M
PM
Nishina
Jürgen K
JK
Naggert
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000818:Animals; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics*; D051379:Mice; D008806:Mice, Inbred AKR; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; C490547:MAP1A protein, mouse; D008869:Microtubule-Associated Proteins; D011506:Proteins; C098988:Tub protein, mouse; C491353:Tulp1 protein, mouse