Nrl (neural retina leucine zipper gene) plays an essential role in rod photoreceptor differentiation and homeostasis. These animals carry a targeted allele in which the entire coding region of the mouse gene has been deleted. This strain may be useful in studies of retinal and macular degenerative diseases.
Anand Swaroop, NIH/NEI
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.
The entire coding region (exons 2 and 3) was replaced with a neomycin resistance cassette. R1 embryonic stem (ES) cells derived from (129X1/SvJ x 129S1/Sv)F1- Kitl+ were used to create the mutation. The donating investigator reported that this strain was backcrossed to C57BL/6J for at least 4-5 generations prior to arrival at The Jackson Laboratory (see SNP note below).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Tweleve markers throughout the genome are segregating for 129 suggesting an incomplete backcross.
|Allele Name||targeted mutation 1, Anand Swaroop|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||cone-full; Nrl-|
|Gene Symbol and Name||Nrl, neural retina leucine zipper gene|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A PGK-neomycin resistance cassette replaced the entire coding region (exons 2 and 3). Immunoblot analysis did not detect protein in retina from 10 day old homozygous mutant mice. RT-PCR studies of retina from 10 day old homozygous mutant mice did not detect mRNA.|
Homozygotes and heterozygotes are viable and fertile.
When using the B6;129-Nrltm1Asw/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021152 in your Materials and Methods section.