huABCA4 Mouse
Product Name
huABCA4 Mouse
Product ID
C001954
Strain Name
C57BL/6JCya-Abca4tm3(hABCA4)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “huABCA4 Mouse (Catalog C001954) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
ABCA4
Gene Alias
FFM, RMP, ABCR, RP19, STGD, ABC10, ARMD2, CORD3, STGD1
NCBI ID
Chromosome
Chr 1 (Human)
MGI ID
Datasheet
Strain Description
Stargardt Disease (STGD) is a hereditary macular dystrophy marked by yellowish fusiform spots in the retinal pigment epithelium, leading to macular atrophy. It primarily affects children and adolescents, causing progressive central vision loss and mild color vision impairment. The fundus may show pale yellow lesions with gold foil-like reflections and yellow-white spots around the posterior pole. Advanced stages involve atrophy of the retinal pigment epithelium, photoreceptor cells, and choriocapillaris. STGD is also common in sporadic cases and more frequent in children of consanguineous marriages. It affects both eyes bilaterally and progresses synchronously without significant gender differences, with an incidence of approximately 1/8000 to 1/13000. STGD is an autosomal recessive retinal disease caused by ABCA4 gene mutations, accounting for 95% of cases [1].
The ABCA4 gene encodes a retina-specific ABC transporter protein that removes retinal derivatives and toxic metabolites after rhodopsin photobleaching. Mutations in ABCA4 lead to the accumulation of these substances, causing apoptosis of retinal pigment epithelial and photoreceptor cells, resulting in retinal degenerative diseases. ABCA4 mutations are linked to Stargardt Disease (STGD), Cone-rod Dystrophy (CRD), and Retinitis Pigmentosa (RP) [2-3]. The clinical phenotype depends on the extent of ABCA4 mutations, with severe and mild mutations or two moderate mutations predisposing to STGD, and one moderate mutation predisposing to CRD.
Currently, the drug pipeline for treating Stargardt disease (STGD) primarily focuses on supplemental delivery methods for ABCA4-targeted drugs. Among them, ProQR has developed a therapeutic antisense oligonucleotide (ASO) drug, QR-1011, which targets the c.5461-10T>C mutation [4]. Most ASO medicines and gene therapies act on the human ABCA4 gene. Considering the genetic differences between animals and humans, modifying mouse genes to be more human-like would help accelerate gene therapies targeting ABCA4 into the clinical stage. This strain is a mouse Abca4 gene humanized model and can be used to research STGD, CRD, and RP. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate mutation (ABCA4 c.5461-10 T to C) models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.
Reference
Roberts L J , Nossek C A , Greenberg L J ,et al.Stargardt macular dystrophy: common ABCA4 mutations in South Africa—establishment of a rapid genetic test and relating risk to patients[J].Molecular Vision, 2012, 18(31-33):280-289.DOI:doi:10.3928/1081597X-20111209-01.
Aukrust, IngvildJansson, Ragnhild W.Bredrup, CecilieRusaas, Hilde E.Berland, SirenJorgensen, AgneteHaug, Marte G.Rodahl, EyvindHouge, GunnarKnappskog, Per M.The intronic ABCA4 c.5461-10T > C variant, frequently seen in patients with Stargardt disease, causes splice defects and reduced ABCA4 protein level[J].Acta ophthalmologica, 2017.
ABCA4 midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease[J].Genome Research, 2018.
Kaltak M, de Bruijn P, Piccolo D, et al. Antisense oligonucleotide therapy corrects splicing in the common Stargardt disease type 1-causing variant ABCA4 c.5461-10T>C. Mol Ther Nucleic Acids. 2023 Feb 18;31:674-688. doi: 10.1016/j.omtn.2023.02.020.
Strain Strategy
The sequences from the ATG start codon to the TGA stop codon of the endogenous mouse Abca4 gene were replaced with the sequences from the ATG start codon to the TGA stop codon of the human ABCA4 gene.
Figure 1. Gene editing strategy for huABCA4 mice.
Application Area
Research on Stargardt Disease (STGD);
Research on Cone-rod Dystrophy (CRD);
Research on Retinitis Pigmentosa (RP).
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