title: Optic nerve axon number in mouse is regulated by PAX2.
abstract: BACKGROUND
  Papillorenal syndrome is an autosomal-dominant disease caused by mutations in the PAX2 transcription factor gene. Patients often exhibit congenital excavation of the optic nerve and a spectrum of congenital kidney abnormalities. Using a novel mouse model of this syndrome (C57BL/6J PAX2(A220G/+)), we investigated the effect of PAX2 haploinsufficiency on optic nerve axon number. Because PAX2 expression and retinal pigment epithelium pigmentation have a mutually exclusive relationship during development and because tyrosinase (Tyr) has been shown to modify the penetrance of other ocular development genes, we also investigated whether tyrosinase modified the mutant PAX2 phenotype.
  
  
  METHODS
  C57BL/6J PAX2(A220G/+)Tyr(+/+) mice were crossed with mice of the same genetic background (C57BL/6J) that are homozygous for an effective null allele of tyrosinase (Tyr(c-2J/c-2J)) over two generations to create mice with four distinct genotypes: PAX2(A220G/+) Tyr(+/c-2J), PAX2(A220G/+) Tyr(c-2J/c-2J), PAX2(+/+) Tyr(c-2J/+), and PAX2(+/+)Tyr(c-2J/c-2J). Mouse optic nerves were examined clinically and histologically. Axon number was assessed in a masked fashion in optic nerves from mice of all four genotypes and compared with parental strains.
  
  
  RESULTS
  Mice heterozygous for a PAX2 mutation show reduced optic nerve axon number compared with age-matched controls. Tyrosinase does not appear to modify this phenotype.
  
  
  CONCLUSIONS
  Our results show that PAX2 is important in determining axon number in mouse optic nerve. The developmental effects of tyrosinase and PAX2 mutation appear to act via different pathways.
authors: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors: Ramakrishna P
authors: RP
authors: Alur
authors: Terry A
authors: TA
authors: Cox
authors: Mary Alice
authors: MA
authors: Crawford
authors: Xiaohua
authors: X
authors: Gong
authors: Brian P
authors: BP
authors: Brooks
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000235:genetics; D009154:Mutation; D009898:Optic Disk / Q000002:abnormalities / Q000473:pathology; D009900:Optic Nerve / Q000002:abnormalities / Q000033:anatomy & histology* / Q000473:pathology; D051762:PAX2 Transcription Factor / Q000235:genetics*
chemical_list: D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; C497319:Pax2 protein, mouse; D014442:Monophenol Monooxygenase