Abcr- mice have a neo cassette replacing the promoter and exon 1 of the ATP-binding cassette, sub-family A (ABC1), member 4 (Abca4) gene, abolishing gene expression. ABCR (ABCA4) is a retina-specific protein localized in outer segment disk edges of rod photoreceptors. Mutations in ABCR have been linked to the onset of macular degenerations such as Stargardt macular dystrophy (STGD), recessive retinitis pigmentosa, recessive cone-rod dystrophy, and age-related macular degeneration (AMD). ABCR acts as a transmembrane flippase transporter for phosphatidylethanolamine (N-Ret-PE) which moves N-Ret-PE from inside of the photoreceptor disks out to the cytoplasmic surface. The retinal pigment epithelium (RPE) of the Abcr- mice accumulates of bis-retinoid-lipofuscin material, which is further amplified after supplementation with Vitamin A. The major bis-retinoid-lipofuscin pigment in the RPE of Abcr-/- mice and STGD1 patients is A2E. The knockout mice exhibit slow-photoreceptor degeneration and delayed dark adaptation following a photobleach. Abcr homozygotes null mice are viable and fertile.
Of note, this allele is also available on a congenic C57BL/6J background (Stock No. 026800).
A targeting vector was designed to replace the promoter and exon 1 of the ATP-binding cassette, sub-family A (ABC1), member 4 (Abca4) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to 129SvEv females. These mice were maintained on a 129SvEv background by the donating lab (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.
In 2020, a 135 SNP analysis (with markers covering all 19 chromosomes and the X chromosome) was performed on mice at The Jackson Laboratory Repository. This showed all markers as 129S allele-type except one marker on Chromosome 6 and one marker on Chromosome 16, which were both segregating with BALB/c from an unknown source. These mice were determined to be 129S congenic (~98.5% 129S).
|Allele Name||targeted mutation 1, Gabriel H Travis|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Abca4, ATP-binding cassette, sub-family A (ABC1), member 4|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Replacement of a 4 kb genomic fragment containing the promoter and first exon with a neomycin cassette. Immunoblot analysis of retinal homogenates failed to detect any protein in samples derived from homozygous mice.|
When maintaining a live colony, homozygous mice may be bred together.
When using the abcr- mouse strain in a publication, please cite the originating article(s) and include JAX stock #023725 in your Materials and Methods section.