Abca4 KO Mice

Catalog Number: I001134

Strain Name: C57BL/6JCya-Abca4^em3/Cya

Genetic Background: C57BL/6JCya

Reproduction: Heterozygote x Heterozygote

Strain Description

Stargardt disease (STGD), a hereditary macular dystrophy, is characterized by the presence of yellowish flecks within the retinal pigment epithelium (RPE), ultimately culminating in macular atrophy. Typically manifesting in childhood and adolescence, STGD leads to progressive central vision loss and mild dyschromatopsia. Fundoscopic examination may reveal pale yellow lesions exhibiting a characteristic gold foil-like sheen, accompanied by yellow-white spots surrounding the posterior pole. In advanced stages, atrophy of the RPE, photoreceptors, and choriocapillaris is observed. This bilateral and typically synchronous condition affects both eyes with comparable incidence across sexes, estimated between 1/8,000 and 1/13,000. STGD is predominantly an autosomal recessive disorder, with mutations in the ABCA4 gene accounting for approximately 95% of cases. ABCA4 encodes a retina-specific ABC transporter protein crucial for the clearance of retinal derivatives and toxic metabolites generated during rhodopsin photobleaching. Consequently, ABCA4 mutations result in the accumulation of these cytotoxic substances, triggering apoptosis of both RPE and photoreceptor cells and ultimately driving retinal degeneration. Notably, ABCA4 mutations have been implicated in a spectrum of retinal diseases, including STGD, cone-rod dystrophy (CRD), age-related macular degeneration (AMD), and retinitis pigmentosa (RP), with the specific clinical phenotype correlating with the nature and severity of the ABCA4 mutation.

This strain is an Abca4 gene knockout (KO) mouse model. Gene-editing technology was used to delete the protein-coding sequence of the Abca4 gene (the homolog of the human ABCA4 gene) in mice. Previous studies have demonstrated that Abca4 KO mice exhibit delayed dark adaptation following photobleaching and a slow progression of photoreceptor degeneration ^[1]. Homozygous Abca4 KO mice are viable and fertile.

Strain Strategy

This strain was created using gene-editing technology to delete the exon 2-49 region.

Application

• Research on Stargardt Disease (STGD);
• Research on Cone-rod Dystrophy (CRD);
• Research on Retinitis Pigmentosa (RP);

Validation Data

1. Expression of Abca4 gene

Figure 1. Abca4 mRNA expression in the liver, eye, kidney, and brain tissues of 6-week-old homozygous Abca4 KO mice and wild-type mice (WT). RT-qPCR results indicate no expression of the mouse Abca4 gene in the liver, eye, kidney, and brain tissues of Abca4 KO mice.

References

[1] Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell. 1999 Jul 9;98(1):13-23.