Modulation of retinal cell populations and eye size in retinoic acid receptor knockout mice

Guomin Zhou, Richelle C. Strom, Vincent Giguere, Robert Williams

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: The retinoic acid receptors are expressed from early stages of development in the diverse tissues that make up the vertebrate eye. Their loss has subtle effects on eye development. We adapted sensitive quantitative trait locus (QTL) mapping methods to assess consequences of inactivating alleles of the alpha and beta receptors, Rara and Rarb, on eye and retinal development. Rara is of particular interest because this gene is a candidate for Nnc1, a QTL that controls retinal ganglion cell proliferation. Methods: We studied lines of mice in which expression of the α1 isoform of Rara or all isoforms of Rarb had been disrupted by gene targeting. We measured eye weight, lens weight, retinal area, and retinal ganglion cell number in each of six genotypes (Rara and Rarb -/-, +/-, +/+; 10-25 cases/genotype). Results: Loss of either protein is associated with a small but significant loss of eye weight and retinal area. However, only the Rarb knockout has a significant effect on the ganglion cell population and the loss of both wildtype alleles leads to an 8,000 cell deficit. Surprisingly, loss of the Rara α1 isoform that is expressed in this cell population from early stages has no effect on number. Null alleles of both genes have little if any effect on lens growth. Conclusions: Despite its expression in embryonic retina, Rara is unlikely to be the Nnc1 QTL. In contrast, Rarb, a gene that maps to Chr 14 and which is not an Nnc1 candidate gene, has a significant effect on cell number and is therefore a QTL controlling this key population. This raises the intriguing possibility that normal allelic variants of Rarb modulate the ganglion cell population in other vertebrates, including humans.

Original languageEnglish (US)
Pages (from-to)253-260
Number of pages8
JournalMolecular Vision
Volume7
StatePublished - Dec 1 2001

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Retinoic Acid Receptors
Quantitative Trait Loci
Population Density
Knockout Mice
Protein Isoforms
Retinal Ganglion Cells
Alleles
Ganglia
Population
Genes
Vertebrates
Cell Count
Genotype
Weights and Measures
Crystalline Lens
Internal-External Control
Gene Targeting
Lenses
Retina
Weight Loss

All Science Journal Classification (ASJC) codes

  • Ophthalmology

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Modulation of retinal cell populations and eye size in retinoic acid receptor knockout mice. / Zhou, Guomin; Strom, Richelle C.; Giguere, Vincent; Williams, Robert.

In: Molecular Vision, Vol. 7, 01.12.2001, p. 253-260.

Research output: Contribution to journalArticle

Zhou, Guomin ; Strom, Richelle C. ; Giguere, Vincent ; Williams, Robert. / Modulation of retinal cell populations and eye size in retinoic acid receptor knockout mice. In: Molecular Vision. 2001 ; Vol. 7. pp. 253-260.
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