Nature Genetics
23, 466 - 470 (1999)
doi:10.1038/70591
Retinopathy and attenuated circadian entrainment in Crx-deficient
miceTakahisa Furukawa1, 4, Eric M. Morrow1, Tiansen Li2, Fred C. Davis3
& Constance L. Cepko11
Department of Genetics and Howard Hughes Medical Institute,
Harvard Medical School, Boston, Massachusetts,
USA. 2
The Berman-Gund Laboratory for the Study of Retinal
Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary
, Boston, Massachusetts, USA. 3
Department of Biology, Northeastern University,
Boston, Massachusetts, USA. 4
Present address: Center for Developmental Biology,
The University of Texas, Southwestern Medical Center at Dallas,
Dallas, Texas, USA.
Correspondence should be addressed to Constance L. Cepko cepko@rascal.med.harvard.edu or Takahisa Furukawa furukawa@utsw.swmed.edu
Crx, an Otx-like homeobox gene, is expressed specifically
in the photoreceptors of the retina and the pinealocytes of the pineal gland1,
2. Crx has been proposed to have a role in the regulation
of photoreceptor-specific genes in the eye and of pineal-specific genes in
the pineal gland. Mutations in human CRX are associated with the retinal
diseases, cone-rod dystrophy-2 (adCRD2; refs 3, 4, 5), retinitis pigmentosa5 (RP) and Leber congenital amaurosis5,
6 (LCA), which
all lead to loss of vision. We generated mice carrying a targeted disruption
of Crx. Crx−/− mice do not elaborate
photoreceptor outer segments and lacked rod and cone activity as assayed by
electroretinogram (ERG). Expression of several photoreceptor- and pineal-specific
genes was reduced in Crx mutants. Circadian entrainment was also affected
in Crx−/− mice.
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