Retinal phenotype of genetically modified ocular retardation mice

C. Bone Larson, S. Basu, M. Burmeister, M. H. Hankin

Research output: Contribution to journalArticle

Abstract

Purpose. Mice carrying the orJ allele of ocular retardation have severe microphthalmia, a thin hypocellular retina and optic nerve aplasia; these mice have a premature stop codon in the homeobox of the Chx10 gene, a gene expressed at high levels in developing neural retina. This mutation leads to reduced proliferation of retinal progenitors, and an absence of differentiated bipolar cells and of a distinct inner nuclear layer (INL). Here mice with a modified phenotype due to a genetic background effect were used to discriminate between primary effects of Chx10, and effects influenced by other factors. Methods. A genetic backcross with a distantly related mouse substrain Mus musculus castaneus [(129/Sv-orJ x CASA/Rk) F1 X 129/Sv-orJ] was used to produce "modified" orJ mice, which were selected for large eyes; brother-sister matings followed by selection for large eyes were performed over at least four generations. Immunohistochemistry was used to assess retinal cell differentiation in the resulting mice. Results. The "modified" orJ mice, which were homozygous for the Chx10 mutation, had eyes of nearly normal size; yet, they were completely blind. Like the 129/Sv-orJ, the adult "modified" orJ neural retina was much thinner than normal and was present primarily in the central portion of the globe, although it was not as severely affected as in 129/Sv-orJ. Like 129/Sv-orJ, the "modified" orJ retina contained differentiated ganglion cells, amacrine cells, Müller glia and rod photoreceptors, but not bipolar cells. In addition, the "modified" orJ mice did not appear to have an optic nerve, but unlike 129/Sv-orJ mice, they did exhibit a distinct INL. Conclusions. These observations suggest that the primary effect of the loss of chx10 is on cell proliferation and differentiation of bipolar cells. The background upon which the orJ allele is carried may modulate the effects of the Chx10 mutation, primarily in the degree to which normal lamination is developed.

Original languageEnglish (US)
Pages (from-to)S327
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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