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 STGD patients is A2E. The knockout mice exhibit slow-photoreceptor degeneration and delayed dark adaptation following a photobleach. Abcr homozygous null mice are viable and fertile.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these C57BL/6J-congenic mice could vary from that originally described on a 129S genetic background. We may modify the strain description if necessary as published results become available.
When crossed to mice homozygous for the Rdh8tm1Kpal allele (Stock No. 017630), the resulting double mutant homozygous mice (Stock No. 030503) exhibit retinal dystrophy, light-dependant progressive retinal degeneration and are a model for age-related macular degeneration.
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 upon arrival at The Jackson Laboratory (as Stock No. 023725). Some mice were bred to C57BL/6J inbred mice (Stock No. 000664) for many generations using a marker-assisted, speed congenic approach to generate this C57BL/6J-congenic strain (Stock No. 026800).
|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.|
Mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for several generations using a marker-assisted, speed congenic approach to establish this congenic strain. When maintaining the live congenic 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 #026800 in your Materials and Methods section.