huUNC13A Mouse
Product Name
huUNC13A Mouse
Product ID
C002069
Strain Name
C57BL/6JCya-Unc13atm1(hUNC13A)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “huUNC13A Mouse (Catalog C002069) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
UNC13A
Gene Alias
Munc13-1
NCBI ID
Chromosome
Chr 19 (Human)
MGI ID
Datasheet
Strain Description
Synaptic vesicle priming factor UNC13A, also known as Munc13-1, is a member of the UNC13 protein family and a critical component of the presynaptic active zone, playing a central role in neurotransmitter release and synaptic transmission. This protein contains C1, C2, and MUN domains, enabling it to specifically mediate the synaptic vesicle priming process and promote the assembly of the SNARE complex. This renders the vesicles in a fusion-ready state, thereby regulating calcium-dependent neurotransmitter release and participating in critical physiological processes such as short-term synaptic plasticity, learning and memory, and the maintenance of neural network excitability [1]. UNC13A is predominantly expressed at high levels in neurons of the central nervous system, with particular enrichment at glutamatergic presynaptic terminals. It can also be detected in certain peripheral nerves and endocrine cells, underscoring its pivotal significance in neural signal transduction and the regulation of synaptic homeostasis [2].
Research indicates that genetic variants and aberrant expression of UNC13A are intimately associated with the pathogenesis and progression of multiple neurological diseases, with its implications in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and neurodevelopmental disorders being particularly prominent [3]. In ALS, the dysfunction of RNA-binding proteins, notably TDP-43, leads to cryptic exon inclusion in UNC13A mRNA. This causes a reduction in functional protein expression, which consequently impairs synaptic transmission and compromises motor neuron survival [4]. In the context of neurodevelopmental disorders, pathogenic UNC13A variants can result in severe epilepsy, intellectual disability, and movement disorders [5]. Given its core function in synaptic dynamics, UNC13A has emerged as a crucial molecular target in the therapeutics of neurodegenerative and neurodevelopmental diseases. Pharmacological modulation strategies—such as the use of antisense oligonucleotides (ASOs) or small molecules—aimed at restoring the normal splicing and expression of UNC13A have demonstrated promising therapeutic potential in ALS models [6-7].
huUNC13A mice are humanized models constructed using gene editing technology. In this model, the sequences from upstream of exon 1 to the partial 3'UTR of mouse Unc13a were replaced with the sequences from upstream of exon 1 to downstream of exon 44 of human UNC13A. huUNC13A mice can be used for preclinical studies investigating the pathogenesis of neurological and psychiatric diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and neurodevelopmental disorders, as well as for the evaluation of UNC13A-targeted therapeutics.
Reference
Reddy-Alla S, Böhme MA, Reynolds E, et al. Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission. Neuron. 2017;95(6):1350-1364.
Böhme MA, Beis C, Reddy-Alla S, et al. Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca(2+) channel-vesicle coupling. Nat Neurosci. 2016;19(10):1311-1320.
Cruchaga C. Integrating functional genomics with genetics to understand the biology of ALS and FTD. Med. 2022;3(4):226-227.
Brown AL, Wilkins OG, Keuss MJ, et al. TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A. Nature. 2022;603(7899):131-137.
Asadollahi R, Ahmad A, Boonsawat P, et al. Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function. Nat Genet. 2025;57(11):2691-2704.
Miller TM, Cudkowicz ME, Genge A, et al. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2022;387(12):1099-1110.
Amado DA, Robbins AB, Whiteman KR, et al. AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice. Nat Commun. 2025;16(1):5334.
Strain Strategy
The sequences from upstream of exon 1 to the partial 3'UTR of the mouse Unc13a were replaced with the sequences from upstream of exon 1 to downstream of exon 44 of the human UNC13A.
Figure 1. Gene editing strategy of huUNC13A mice.
Application Area
The screening, development, and preclinical evaluation of UNC13A-targeted drugs;
Research on the pathogenesis and therapies of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD);
Research on the pathogenesis and therapies of neurodevelopmental disorders.
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