C57BL/6JCya-Ano4em1/Cya
Common Name:
Ano4-KO
Product ID:
S-KO-09236
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Ano4-KO
Strain ID
KOCMP-320091-Ano4-B6J-VA
Gene Name
Product ID
S-KO-09236
Gene Alias
A330096O15Rik; Gm65; Tmem16d
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
10
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Ano4em1/Cya mice (Catalog S-KO-09236) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000182341
NCBI RefSeq
NM_001277188.1
Target Region
Exon 4
Size of Effective Region
~1.0 kb
Detailed Document
Overview of Gene Research
Ano4, also known as TMEM16D, belongs to the anoctamin family of Ca2+-activated proteins. It functions as a Ca2+-dependent non-selective cation channel [4]. It is involved in multiple biological processes such as regulating aldosterone secretion in the zona glomerulosa of the human adrenal gland, and may play a role in Ca2+ signaling, as well as in the function of glucose-inhibited neurons in the ventromedial hypothalamus [3,4,5]. It has also been associated with ADAM-dependent cellular functions through its scramblase activity [6]. Genetic models are valuable for studying its function.
Missense variants in Ano4 have been linked to fever-sensitive developmental and epileptic or epileptic encephalopathy, as well as generalized epilepsy with febrile seizures plus or temporal lobe epilepsy. In silico modeling predicted these variants would destabilize the Ano4 structure, and functional studies in a heterologous expression system showed a severe loss of ion channel function and some loss of surface expression due to impaired plasma membrane trafficking. Co-transfection with wild-type Ano4 suggested a dominant-negative effect [1]. In non-metastasized clear cell renal cell carcinoma, low Ano4 expression is associated with advanced clinicopathological variables and shorter survival, and gene set enrichment analysis identified several enriched pathways within the low-expression group [2]. In the context of Alzheimer's disease, deletion of oligodendrocyte Bace1 in APPNL-G-F/wt knock-in mice increased Ano4 expression along with other genes associated with Aβ generation and clearance [7].
In conclusion, Ano4 is a multifunctional protein involved in ion channel activity, aldosterone regulation, and neuronal function. Its missense variants are associated with epileptic disorders. In cancer, its expression levels have prognostic significance, and in Alzheimer's disease, it may be involved in amyloid-related processes. Gene knockout or knockdown models, either directly targeting Ano4 or indirectly affecting its expression, have been crucial in revealing its role in these disease-related biological processes [1,2,7].
References:
1. Yang, Fang, Begemann, Anais, Reichhart, Nadine, Strauß, Olaf, Rauch, Anita. 2024. Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect. In American journal of human genetics, 111, 1184-1205. doi:10.1016/j.ajhg.2024.04.014. https://pubmed.ncbi.nlm.nih.gov/38744284/
2. Al Sharie, Ahmed H, Al Zu'bi, Yazan O, El-Elimat, Tamam, Al Malkawi, Abubaker A, Alali, Feras Q. 2023. ANO4 Expression Is a Potential Prognostic Biomarker in Non-Metastasized Clear Cell Renal Cell Carcinoma. In Journal of personalized medicine, 13, . doi:10.3390/jpm13020295. https://pubmed.ncbi.nlm.nih.gov/36836529/
3. Maniero, Carmela, Scudieri, Paolo, Haris Shaikh, Lalarukh, Galietta, Luis J V, Brown, Morris J. 2019. ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion. In Hypertension (Dallas, Tex. : 1979), 74, 1152-1159. doi:10.1161/HYPERTENSIONAHA.119.13287. https://pubmed.ncbi.nlm.nih.gov/31564164/
4. Reichhart, Nadine, Schöberl, Simon, Keckeis, Susanne, Schellenberger, Eyk, Strauß, Olaf. 2019. Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel. In Scientific reports, 9, 2257. doi:10.1038/s41598-018-37287-y. https://pubmed.ncbi.nlm.nih.gov/30783137/
5. Tu, Longlong, Bean, Jonathan C, He, Yang, He, Yanlin, Xu, Yong. 2023. Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia. In The Journal of clinical investigation, 133, . doi:10.1172/JCI163391. https://pubmed.ncbi.nlm.nih.gov/37261917/
6. Leitzke, Sinje, Seidel, Jana, Ahrens, Björn, Bhakdi, Sucharit, Reiss, Karina. 2022. Influence of Anoctamin-4 and -9 on ADAM10 and ADAM17 Sheddase Function. In Membranes, 12, . doi:10.3390/membranes12020123. https://pubmed.ncbi.nlm.nih.gov/35207044/
7. Ishii, Akihiro, Pathoulas, Joseph A, MoustafaFathy Omar, Omar, Yan, Riqiang, Hu, Xiangyou. 2024. Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer's disease. In Molecular neurodegeneration, 19, 83. doi:10.1186/s13024-024-00759-z. https://pubmed.ncbi.nlm.nih.gov/39548583/
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