STOCK Sag^tm1Jnc/J

Stock number: 013197
Research areas: Research Tools, Sensorineural Research

Description

This visual arrestin knock out mouse strain may be useful in studies of photoreceptor adaptation, phototransduction, and retinopathy.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These mutant mice are photosensitive and if not maintained under low light conditions will develop progressive retinal degeneration. No gene product (protein) is detected by Northern blot analysis of retinas from homozygous mice maintained in cyclic (12 hour light: 12 hour dark) conditions. Photoreceptor loss in homozygotes maintained in cyclic light conditions begins at approximately 100 days of age, progressing to loss of more than half of the photoreceptors by 1 year of age. After 1 week of constant light exposure, homozygotes lose 30% of photoreceptors; after 3 weeks of constant light exposure, more than 60% of photoreceptors are lost. Homozygotes maintained under cyclic light conditions exhibit disorganized and 25% shorter retinal rod outer segment layer, as well as reduced levels of retinal rhodopsin. Recovery phase response to light flash stimulation of the retina is significantly longer in homozygotes, although light adaptation function is normal.

IMPORTANT NOTE: Breeding colonies at The Jackson Laboratory are maintained in normal light conditions. We will attempt to maintain this colony in shelf positions that allow the least amount of light possible (i.e., lower shelves), but can not guarantee the extent of retinal damage (if any) in the mice we provide. For experimental use, we strongly suggest investigators use the mice we provide for breeding purposes rather than experiments. This allows each investigator to generate their own experimental offspring in light conditions ideal for their own respective experiments.

Development

A targeting vector containing MC1neopA cassette was used to disrupt part of the 5' promoter and exons 1 and 2. The construct was electroporated into 129/SvEv derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The donating investigator reports these mice were then backcrossed to C57BL/6 for five generations (see SNP results below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

In March 2011, a 32 SNP (single nucleotide polymorphism) panel analysis with markers covering all 19 chromosomes and the X chromosome was performed on the first generation of rederived mice at The Jackson Laboratory Repository. This revealed markers that were not C57BL/6 allele-type at nine loci (representing seven different chromosomes: 1, 3, 6, 8, 12, 13, and 17). The marker on chromosome 17 (~34 Mbp) is neither C57BL/6 nor 129S allele-type. The other eight markers may be 129S (or other) allele-type. These data suggest the mice sent to The Jackson Laboratory Repository were not fully backcrossed onto the C57BL/6 genetic background, and are on a more mixed genetic background of C57BL/6 and 129S with contributions from either A, C3H/He, SJL, SWR, and/or other unknown lines. Furthermore, this data might suggest the mice are on a mixed C57BL/6;129S genetic background with some other contamination on chromosome 17 (that may or may not affect the MHC genes).

Allele

Symbol: Sag^tm1Jnc
Name: targeted mutation 1, Jeannie Chen
MGI accession ID: MGI:2388373
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: arr1-; Arrb1^tm1Jnc; arrestin^-
Marker symbol: Sag
Marker name: S-antigen, retina and pineal gland (arrestin)
Marker synonyms: A930001K18Rik; Arr1; arrestin 1; rod arrestin; RP47; RP96; S-AG; SAGMR; SANTI; visual arrestin 1
Chromosome: 1
Strain of origin: 129S/SvEv
Molecular note: Part of the 5' promoter and exons 1 and 2 were replaced with a neomycin resistance cassette via homologous recombination. Gene expression was undetectable in rod cells of homozygous mutant animals as shown by Western blot analysis.