C57BL/6JCya-Whrnem1flox/Cya
Common Name:
Whrn-flox
Product ID:
S-CKO-15769
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Whrn-flox
Strain ID
CKOCMP-73750-Whrn-B6J-VA
Gene Name
Product ID
S-CKO-15769
Gene Alias
1110035G07Rik; C430046P22Rik; Dfnb31; Ush2d; wi
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
4
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Whrnem1flox/Cya mice (Catalog S-CKO-15769) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000084510
NCBI RefSeq
NM_001008791
Target Region
Exon 4
Size of Effective Region
~0.8 kb
Detailed Document
Overview of Gene Research
WHRN, also associated with DFNB31, is a gene encoding a cytoskeletal scaffold protein. It binds membrane protein complexes to the cytoskeleton in ocular photoreceptors and ear hair cell stereocilia. WHRN is part of the ankle-link complex (ALC), which is crucial for hair cell development [2,3,5]. Mutations in WHRN are linked to non-syndromic hearing loss and Usher syndrome type II, making it significant in understanding auditory and vestibular function and associated disorders [1,3,4].
In a Moroccan family with severe hearing loss, whole exome sequencing identified a homozygous mutation in WHRN (c.619G>T; p.Ala207Ser). Bioinformatics methods predicted pathogenic implications of this variation [3]. Adgrv1 Y6236fsX1 mutant mice, a model of a human deafness-associated mutation, showed that the Y6236fsX1 mutation disrupts the interaction between ADGRV1 and other ALC components including WHRN, leading to stereocilia disorganization and mechanoelectrical transduction deficits. ADGRV1 normally inhibits WHRN phosphorylation through regional cAMP-PKA signaling, which regulates the ubiquitination and stability of USH2A, but this is disrupted in the mutant [2]. Also, different isoforms of WHRN (WHRN-L and WHRN-S) have distinct localizations within stereocilia and across hair cell types. Lack of both isoforms causes abnormally short stereocilia, profound deafness, and vestibular dysfunction, while WHRN-S alone can maintain some hair cell function [6].
In conclusion, WHRN plays a vital role in the development and function of ear hair cells and is associated with auditory and vestibular phenotypes. The study of WHRN through gene-based mouse models has provided insights into the mechanisms of hearing loss and Usher syndrome type II, highlighting its importance in understanding the pathophysiology of these diseases [2,3,6].
References:
1. Castiglione, Alessandro, Möller, Claes. 2022. Usher Syndrome. In Audiology research, 12, 42-65. doi:10.3390/audiolres12010005. https://pubmed.ncbi.nlm.nih.gov/35076463/
2. Guan, Ying, Du, Hai-Bo, Yang, Zhao, Sun, Jin-Peng, Xu, Zhi-Gang. 2023. Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2205993. doi:10.1002/advs.202205993. https://pubmed.ncbi.nlm.nih.gov/37066759/
3. AitRaise, Imane, Amalou, Ghita, Redouane, Salaheddine, Petit, Christine, Barakat, Abdelhamid. 2023. Novel pathogenic WHRN variant causing hearing loss in a moroccan family. In Molecular biology reports, 50, 10663-10669. doi:10.1007/s11033-023-08901-8. https://pubmed.ncbi.nlm.nih.gov/37924449/
4. Delmaghani, Sedigheh, El-Amraoui, Aziz. 2022. The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification. In Human genetics, 141, 709-735. doi:10.1007/s00439-022-02448-7. https://pubmed.ncbi.nlm.nih.gov/35353227/
5. Wang, Huang, Du, Haibo, Ren, Rui, Xu, Zhigang, Lu, Qing. 2023. Temporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation. In Nature communications, 14, 1657. doi:10.1038/s41467-023-37267-5. https://pubmed.ncbi.nlm.nih.gov/36964137/
6. Ebrahim, Seham, Ingham, Neil J, Lewis, Morag A, Pass, Johanna C, Steel, Karen P. 2016. Alternative Splice Forms Influence Functions of Whirlin in Mechanosensory Hair Cell Stereocilia. In Cell reports, 15, 935-943. doi:10.1016/j.celrep.2016.03.081. https://pubmed.ncbi.nlm.nih.gov/27117407/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen