Nrl (neural retina leucine zipper gene) encodes a retinal transcription factor that plays an essential role in rod photoreceptor differentiation and homeostasis. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases.
These animals carry a targeted allele in which the entire coding region of the mouse gene has been deleted. Homozyous knockouts are morphologically normal, viable and fertile, but show a complete loss of rod function and super-normal cone function. The photoreceptors have cone-like nuclear morphology and short, sparse outer segments with abnormal disks. Retinas undergo a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. Cone degeneration stabilizes by 4 months of age, resulting in a thinner but intact outer nuclear layer with residual cones expressing S- and M-opsins and preserved photopic electroretinogram.
Homozyous Nrl mutant mice show no Nr2e3 (nuclear receptor subfamily 2, group E, member 3) expression in the retina, demonstrating that Nrl is upstream in pathways leading the development of photoreceptors.
