B6.Cg-Nr2e3^rd7/J

Stock number: 004643
Research areas: Sensorineural Research

Description

In mice homozygous for Nr2e3^rd7, evenly distributed white spots cover the retina and have been detected by Fundus examination as early as 16.5 days of age. Nr2e3 is a retinal transcription factor important in the developmental pathways of photoreceptor cells. Enhanced S-cone syndrome has been associated with mutations in human NR2E3 and mice homozygous for the Nr2e3^rd7 mutation offer a model for this disease.

Detailed description

Nr2e3 is a retinal transcription factor important in the developmental pathways of photoreceptor cells. In mice homozygous for Nr2e3^rd7, evenly distributed white spots cover the retina and have been detected by Fundus examination as early as 16.5 days of age. Whorls and rosettes in the outer nuclear layer can first be detected at 12.5 days of age, before the eyes open. These whorls likely underlie the appearance of the white spots on the retina and the white spots and whorls are both present at one month of age then are reduced in number by 5 months, and disappear by 16 months. Electroretinographs give normal signals until 5 months of age when both rod and cone signals begin to show a progressive reduction. Attenuated retinal vessels and mottled pigment are found by 16 months of age, and the outer nuclear layer is only half normal thickness subsequent to progressive loss of cones and rods. Immunohistochemical assessment revealed that the whorls are filled with and surrounded by cone cells and there is an increase in the percentage of blue opsin expressing cone cells. Thus, NR2E3 regulates photoreceptor cell differentiation. Enhanced S-cone syndrome has been associated with mutations in human NR2E3 and mice homozygous for the Nr2e3^rd7 mutation offer a model for this disease. (Chang et al., 1998; Akhmedov et al., 2000; Haider et al., 2000 and 2001.)

Development

The 77-2 line was developed to carry multiple pigment dilution mutations and several sublines resulted from this. The Nr2e3^rd7 mutation was identified in the subline named "77-2C2a-special", which was not characterized for the alleles it carried but may have had a, Tyrp1^b, Myo5a^d, Hsp6^ru, Tyr^c-ch, and Hsp5^mr. The coat color of "77-2C2a-special" was similar to albino. STOCK-Nr2e3^rd7 (stock #002139) was frozen in 1994 via sibling mating. Nr2e3^rd7 has been backcrossed from the STOCK background onto the C57BL/6J background via the backcross-intercross breeding scheme yielding the strain B6.Cg-Nr2e3^rd7 (stock #004643) which was bred to homozygosity at N8 in the beginning of 2003.

Allele

Symbol: Nr2e3^rd7
Name: retinal degeneration 7
MGI accession ID: MGI:1859180
Generation method: Spontaneous
Attributes: Null/Knockout
Synonyms: rd7
Marker symbol: Nr2e3
Marker name: nuclear receptor subfamily 2, group E, member 3
Marker synonyms: ESCS; photoreceptor-specific nuclear receptor; Pnr; rd7; RNR; RP37
Chromosome: 9
Strain of origin: Not Specified
Molecular note: Conflicting reports exist on the nature of the molecular mutation in this gene. According to one report, this mutation is a deletion of exons 4 and 5, resulting in the absence of 380 bp from the transcript. The predicted protein expressed from this allele would lack 127 amino acids including sequences corresponding to the DNA binding domain. The deletion also introduces a frameshift and creates a premature stop codon. A second report states that an antisense insertion of L1 into exon5 prevents the excision of intron 5 and blocks the release of precursor from its site of synthesis. For details, see the associated references.