Nature Genetics
29, 447 - 452 (2001)
Published online: 5 November 2001; | doi:10.1038/ng774
Nrl is required for rod photoreceptor developmentAlan J. Mears1, Mineo Kondo1, 2, Prabodha K. Swain1, Yuichiro Takada1, Ronald A. Bush1, Thomas L. Saunders3, Paul A. Sieving1, 4
& Anand Swaroop1, 31
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA. 2
Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan 466-8550. 3
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA. 4
National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Correspondence should be addressed to Anand Swaroop swaroop@umich.eduThe protein neural retina leucine zipper (Nrl) is a basic motif−leucine zipper transcription factor that is preferentially expressed in rod photoreceptors1,
2. It acts synergistically with Crx to regulate rhodopsin transcription3,
4,
5. Missense mutations in human NRL have been associated with autosomal dominant retinitis pigmentosa6,
7. Here we report that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones. The photoreceptors in the Nrl
-/- retina have cone-like nuclear morphology8 and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl
-/- retina. On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3.
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