huUSH2A(E10-15)-c.2286_2287insT Mouse
Product Name
huUSH2A(E10-15)-c.2286_2287insT Mouse
Product ID
C001961
Strain Name
C57BL/6JCya-Ush2atm4(hUSH2A*c.2286_2287insT)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “huUSH2A(E10-15)-c.2286_2287insT Mouse (Catalog C001961) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
USH2A
Gene Alias
US2, RP39, USH2, dJ1111A8.1
NCBI ID
Chromosome
Chr 1 (Human)
MGI ID
Datasheet
Strain Description
The USH2A gene encodes Usherin, a protein featuring laminin EGF-like, pentraxin, and fibronectin type III domains, predominantly expressed in the basement membrane of the inner ear and retina. Usherin plays a critical role in developing hair cells in the inner ear, auditory signal transduction, and the maintenance of adhesion via interactions with fibronectin in the retinal basement membrane. Mutations in the USH2A gene disrupt the normal development and function of hair cells, impair fibronectin assembly, and compromise the adhesive properties of the retinal basement membrane, leading to hearing loss and RP symptoms. The USH2A gene is the primary causative gene for Usher syndrome Type II (USH2), with 75%–90% of USH2 cases linked to mutations in this gene [1]. The mutations mainly cause frameshift and premature termination codons, producing a protein that is 85% truncated compared to the normal transcript size, leading to the loss of Usherin protein function [2-5]. Currently, there are no effective therapies for Usher syndrome. Ongoing research focuses on elucidating the genetic mechanisms underlying the disorder and developing gene-based therapeutic strategies.
huUSH2A(E10-15)-c.2286_2287insT mice are obtained by introducing the c.2286_2287insT mutation into the exon 13 of the human USH2A gene in huUSH2A(E10-15) mice (Catalog Number: C001554) using gene editing technology. This model can be used to study the mechanisms and therapeutic approaches for diseases such as Usher syndrome Type II.
Reference
McGee TL, Seyedahmadi BJ, Sweeney MO, Dryja TP, Berson EL. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. J Med Genet. 2010 Jul;47(7):499-506.
Pendse ND, Lamas V, Pawlyk BS, Maeder ML, Chen ZY, Pierce EA, Liu Q. In Vivo Assessment of Potential Therapeutic Approaches for USH2A-Associated Diseases. Adv Exp Med Biol. 2019;1185:91-96. doi: 10.1007/978-3-030-27378-1_15. PMID: 31884594.
Yan D, Ouyang X, Patterson DM, Du LL, Jacobson SG, Liu XZ. Mutation analysis in the long isoform of USH2A in American patients with Usher Syndrome type II. J Hum Genet. 2009 Dec;54(12):732-8. doi: 10.1038/jhg.2009.107. Epub 2009 Oct 30. PMID: 19881469; PMCID: PMC4511341.
Dreyer B, Tranebjaerg L, Brox V, Rosenberg T, Möller C, Beneyto M, Weston MD, Kimberling WJ, Cremers CW, Liu XZ, Nilssen O. A common ancestral origin of the frequent and widespread 2299delG USH2A mutation. Am J Hum Genet. 2001 Jul;69(1):228-34. doi: 10.1086/321269. Epub 2001 Jun 8. Erratum in: Am J Hum Genet 2001 Oct;69(4):922. PMID: 11402400; PMCID: PMC1226039.
Dulla K, Slijkerman R, van Diepen HC, Albert S, Dona M, Beumer W, Turunen JJ, Chan HL, Schulkens IA, Vorthoren L, den Besten C, Buil L, Schmidt I, Miao J, Venselaar H, Zang J, Neuhauss SCF, Peters T, Broekman S, Pennings R, Kremer H, Platenburg G, Adamson P, de Vrieze E, van Wijk E. Antisense oligonucleotide-based treatment of retinitis pigmentosa caused by USH2A exon 13 mutations. Mol Ther. 2021 Aug 4;29(8):2441-2455. doi: 10.1016/j.ymthe.2021.04.024. Epub 2021 Apr 23.
Strain Strategy
The start codon (ATG) of the mouse Ush2a gene is located in exon 1, whereas the start codon (ATG) of the human USH2A gene resides in exon 2. Consequently, exons 10–15 of the human USH2A gene correspond to exons 9–14 of the mouse Ush2a gene. Exons 9 to 14 of the mouse Ush2a gene and their flanking sequences were replaced by exons 10 to 15 of the human USH2A gene and their respective flanking sequences. The c.2286_2287insT mutation was introduced into exon 13 of the human USH2A.
Figure 1. Schematic representation of the gene-editing strategy for the huUSH2A(E10-15) mouse model.
Figure 2. Diagram of the gene editing strategy for the generation of huUSH2A(E10-15)-c.2286_2287insT mice.
Application Area
Research on the pathogenic mechanism of Usher syndrome (USH) and preclinical evaluation of therapeutic drugs;
Development, screening, and preclinical evaluation of USH2A-targeted drugs.
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