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.
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-deficientmice. 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.
Authors: C Ayuso; M J Trujillo; M Robledo; C Ramos; J Benitez; F Martín-Osés; T del Rio; B García-Sandoval Journal: Hum Genet Date: 1996-07 Impact factor: 4.132
Authors: A Ikeda; Q Y Zheng; P Rosenstiel; T Maddatu; A R Zuberi; D C Roopenian; M A North; J K Naggert; K R Johnson; P M Nishina Journal: Hum Mol Genet Date: 1999-09 Impact factor: 6.150
Authors: Thomas Langmann; Silvio Alessandro Di Gioia; Isabella Rau; Heidi Stöhr; Nela S Maksimovic; Joseph C Corbo; Agnes B Renner; Eberhart Zrenner; Govindasamy Kumaramanickavel; Marcus Karlstetter; Yvan Arsenijevic; Bernhard H F Weber; Andreas Gal; Carlo Rivolta Journal: Am J Hum Genet Date: 2010-08-12 Impact factor: 11.025
Authors: Fabian Runkel; Heinrich Büssow; Kevin L Seburn; Gregory A Cox; Diane McVey Ward; Jerry Kaplan; Thomas Franz Journal: Mamm Genome Date: 2006-03-03 Impact factor: 2.957
Authors: Quansheng Xi; Gayle J T Pauer; Sherry L Ball; Mary Rayborn; Joe G Hollyfield; Neal S Peachey; John W Crabb; Stephanie A Hagstrom Journal: Invest Ophthalmol Vis Sci Date: 2007-06 Impact factor: 4.799
Authors: Jungyeon Won; Jeremy R Charette; Vivek M Philip; Timothy M Stearns; Weidong Zhang; Jürgen K Naggert; Mark P Krebs; Patsy M Nishina Journal: Exp Eye Res Date: 2013-11-04 Impact factor: 3.467
Authors: Gregory H Grossman; Lindsey A Ebke; Craig D Beight; Geeng-Fu Jang; John W Crabb; Stephanie A Hagstrom Journal: Vis Neurosci Date: 2013-06-10 Impact factor: 3.241
Authors: Douglas Vollrath; Douglas Yasumura; Gillie Benchorin; Michael T Matthes; Wei Feng; Natalie M Nguyen; Cecilia D Sedano; Melissa A Calton; Matthew M LaVail Journal: PLoS Genet Date: 2015-12-11 Impact factor: 5.917
Authors: Song Yi Youn; Hyehyun Min; Se Rok Jeong; Jiahn Lee; Seok Jun Moon; Jinwoong Bok; Chul Hoon Kim Journal: Mol Brain Date: 2022-09-14 Impact factor: 4.399
Authors: Gayle B Collin; Navdeep Gogna; Bo Chang; Nattaya Damkham; Jai Pinkney; Lillian F Hyde; Lisa Stone; Jürgen K Naggert; Patsy M Nishina; Mark P Krebs Journal: Cells Date: 2020-04-10 Impact factor: 7.666