huAIPL1-FLAG-W278* Mouse
Product Name
huAIPL1-FLAG-W278* Mouse
Product ID
C002131
Strain Name
C57BL/6Cya-Aipl1em1(FLAG tag-hAIPL1*W278X)/Cya
Background
C57BL/6Cya
Status
Citations
0
When using this mouse strain in a publication, please cite “huAIPL1-FLAG-W278* Mouse (Catalog C002131) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Standard products are sold as live mice derived from cryorecovery or expansion. Frozen materials are available upon request. Pricing and lead times depend on real-time inventory.
Gene Name
AIPL1
Gene Alias
LCA4, AIPL2
NCBI ID
Chromosome
Chr 17 (Human)
MGI ID
Datasheet
Strain Description
Leber congenital amaurosis (LCA) is a severe inherited blinding retinal disease, accounting for approximately 5% of all inherited retinal diseases. Its global prevalence is approximately 1/80,000 to 1/30,000, and it is one of the blinding eye diseases that causes rapid visual decline after birth. LCA is the earliest-onset and most severe inherited retinal dystrophy. In patients, cone and rod photoreceptor function is completely lost at birth or within the first year of life, resulting in congenital blindness in infants and following an autosomal recessive inheritance pattern. LCA has been classified into at least 17 subtypes, among which AIPL1 gene mutations cause LCA type 4, accounting for approximately 5%–10% of LCA cases [1-2]. AIPL1 encodes aryl hydrocarbon receptor-interacting protein-like 1, which acts as an HSP90 co-chaperone in retinal photoreceptors and is essential for the proper assembly of the rod phototransduction cascade. The truncated protein produced by the W278* mutation lacks the C-terminal TPR domain and is unable to bind HSP90, leading to impaired PDE6 folding and cGMP accumulation, which in turn causes photoreceptor apoptosis and ultimately results in LCA4 [3-6]. Currently, no approved therapy is available for LCA4. Readthrough drugs targeting nonsense mutations have shown potential to restore full-length protein in patient-derived retinal organoids, and adenine base editing has also achieved correction of such variants in patient cell and organoid models [7-8]. Furthermore, AIPL1 variants can cause severe retinal dystrophy with childhood onset, and missense variants that retain partial protein function result in relatively milder phenotypes [9].
The huAIPL1-FLAG-W278* mouse is a humanized model constructed by gene editing technology. The sequence of the endogenous mouse Aipl1 gene from the start codon to the stop codon is replaced with the sequence of the human AIPL1 gene from the start codon to the stop codon, while the p.W278* (TGG to TGA) mutation is introduced into exon 6 of the human AIPL1 gene and a FLAG tag is inserted downstream of the start codon. This model can be used for studying the pathogenesis of LCA4 and the process of photoreceptor degeneration, as well as for screening, development, and preclinical in vivo evaluation of AIPL1-targeted therapies.
Reference
den Hollander AI, et al. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res. 2008;27(4):391-419.
Dharmaraj S, et al. The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations. Arch Ophthalmol. 2004;122(7):1029-1037.
Sohocki MM, et al. Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis. Nat Genet. 2000;24(1):79-83.
Hidalgo-de-Quintana J, et al. The Leber congenital amaurosis protein AIPL1 functions as part of a chaperone heterocomplex. Invest Ophthalmol Vis Sci. 2008;49(7):2878-2887.
Yadav RP, et al. Molecular insights into the maturation of phosphodiesterase 6 by the specialized chaperone complex of HSP90 with AIPL1. J Biol Chem. 2022;298(3):101620.
Sacristan-Reviriego A, et al. The integrity and organization of the human AIPL1 functional domains is critical for its role as a HSP90-dependent co-chaperone for rod PDE6. Hum Mol Genet. 2017;26(22):4465-4480.
Leung A, et al. Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis. Stem Cell Reports. 2022;17(10):2187-2202.
Leung A, et al. Adenine base editor correction of pathogenic variations associated with inherited retinal dystrophy in patient iPSC and retinal organoids. Mol Ther Nucleic Acids. 2025;36(4):102777.
Zhang Q, et al. Clinical and Molecular Characterization of AIPL1-Associated Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy. Am J Ophthalmol. 2024;266:235-247.
Strain Strategy
The sequence from the start codon to the stop codon of the endogenous mouse Aipl1 gene was replaced with the sequence from the start codon to the stop codon of the human AIPL1 gene. The p.W278* (TGG to TGA) point mutation was introduced into exon 6 of the human AIPL1 gene, and the FLAG tag was inserted downstream of the start codon.
Figure 1. Gene editing strategy of huAIPL1-FLAG-W278* mice.
Application Area
Research on the pathogenic mechanisms of Leber congenital amaurosis type 4 (LCA4) and the progression of photoreceptor degeneration;
Screening, development, and preclinical in vivo evaluation of AIPL1-targeted therapies.
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