C57BL/6JCya-Whrnem1/Cya
Common Name:
Whrn-KO
Product ID:
S-KO-19448
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Whrn-KO
Strain ID
KOCMP-73750-Whrn-B6J-VB
Gene Name
Product ID
S-KO-19448
Gene Alias
1110035G07Rik; C430046P22Rik; Dfnb31; Ush2d; wi
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
4
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Whrnem1/Cya mice (Catalog S-KO-19448) 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, a gene encoding a cytoskeletal scaffold protein, is crucial as it binds membrane protein complexes to the cytoskeleton in ocular photoreceptors and ear hair cell stereocilia [2]. It is part of the ankle-link complex (ALC) along with USH2A, PDZD7, and ADGRV1, which is essential for hair cell development [1,3]. Mutations in Whrn are associated with non-syndromic hearing loss and Usher syndrome type II [2].
In Adgrv1 Y6236fsX1 mutant mice (a model for human deafness-associated mutation), the 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, regulating USH2A ubiquitination and stability, but the mutant ADGRV1 Y6236fsX1 fails to do so [1]. Also, different isoforms of Whrn (long and short) have distinct localizations within stereocilia and across hair cell types. Lack of both isoforms in mutants causes abnormally short stereocilia, profound deafness, and vestibular dysfunction, while the short isoform alone can maintain some auditory response and no overt vestibular dysfunction [4].
In conclusion, Whrn plays a vital role in the development and function of hair cells in the inner ear and in maintaining the structure of ocular photoreceptors. Studies using mouse models have revealed its significance in processes related to hearing and vision, with mutations in Whrn being linked to Usher syndrome type II and non-syndromic hearing loss, providing insights into the disease mechanisms and potential therapeutic targets.
References:
1. 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/
2. 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/
3. 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/
4. 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