C57BL/6JCya-Unc13aem1/Cya
Common Name:
Unc13a-KO
Product ID:
S-KO-19029
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Unc13a-KO
Strain ID
KOCMP-382018-Unc13a-B6J-VA
Gene Name
Product ID
S-KO-19029
Gene Alias
2410078G03Rik; Munc13-1
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
8
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Unc13aem1/Cya mice (Catalog S-KO-19029) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000030170
NCBI RefSeq
NM_001029873
Target Region
Exon 4~8
Size of Effective Region
~3.0 kb
Detailed Document
Overview of Gene Research
Unc13a, without common aliases indicated in the references, is a gene expressed in neuronal tissue. It is involved in maintaining synaptic active zones, enabling the priming and docking of synaptic vesicles, which is crucial for neurotransmission [1,2,3,4].
Genome-wide association studies (GWAS) have shown that a polymorphism (rs12608932) in the UNC13A gene is associated with risk for both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) [1]. In the absence of functional TDP-43, risk variants in UNC13A lead to the inclusion of a cryptic exon in its messenger RNA, causing nonsense-mediated decay and loss of functional protein. Depletion of UNC13A leads to impaired neurotransmission [1]. TDP-43 depletion in cultured cells, and in brains and spinal cords from patients with ALS and FTD, induces robust inclusion of a cryptic exon in UNC13A, resulting in nonsense-mediated decay and loss of UNC13A protein. Two common intronic UNC13A polymorphisms strongly associated with these diseases overlap with TDP-43 binding sites and potentiate cryptic exon inclusion [2]. Also, loss of TDP-43 from the nucleus in human brain, neuronal cell lines and motor neurons derived from induced pluripotent stem cells led to the inclusion of a cryptic exon in UNC13A mRNA and reduced UNC13A protein expression [3].
In conclusion, Unc13a is essential for synaptic function, specifically in the processes of vesicle priming and docking for neurotransmission. Studies, especially those related to the loss-of-function scenarios due to TDP-43 depletion and associated polymorphisms, have revealed its crucial role in ALS and FTD. These findings provide potential therapeutic targets for TDP-43 proteinopathies [1,2,3].
References:
1. Willemse, Sean W, Harley, Peter, van Eijk, Ruben P A, Fratta, Pietro, van Es, Michael A. 2023. UNC13A in amyotrophic lateral sclerosis: from genetic association to therapeutic target. In Journal of neurology, neurosurgery, and psychiatry, 94, 649-656. doi:10.1136/jnnp-2022-330504. https://pubmed.ncbi.nlm.nih.gov/36737245/
2. Brown, Anna-Leigh, Wilkins, Oscar G, Keuss, Matthew J, Ward, Michael E, Fratta, Pietro. 2022. TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A. In Nature, 603, 131-137. doi:10.1038/s41586-022-04436-3. https://pubmed.ncbi.nlm.nih.gov/35197628/
3. Ma, X Rosa, Prudencio, Mercedes, Koike, Yuka, Petrucelli, Leonard, Gitler, Aaron D. 2022. TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A. In Nature, 603, 124-130. doi:10.1038/s41586-022-04424-7. https://pubmed.ncbi.nlm.nih.gov/35197626/
4. Keuss, Matthew J, Harley, Peter, Ryadnov, Eugeni, Burrone, Juan, Fratta, Pietro. 2024. Loss of TDP-43 induces synaptic dysfunction that is rescued by UNC13A splice-switching ASOs. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.06.20.599684. https://pubmed.ncbi.nlm.nih.gov/38979232/
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