C57BL/6JCya-Hgsnatem1flox/Cya
Common Name:
Hgsnat-flox
Product ID:
S-CKO-18836
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Hgsnat-flox
Strain ID
CKOCMP-52120-Hgsnat-B6J-VB
Gene Name
Product ID
S-CKO-18836
Gene Alias
9430010M12Rik; D8Ertd354e; Tmem76
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
8
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Hgsnatem1flox/Cya mice (Catalog S-CKO-18836) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000037609
NCBI RefSeq
NM_029884
Target Region
Exon 3~4
Size of Effective Region
~1.8 kb
Detailed Document
Overview of Gene Research
Hgsnat, or heparan-α-glucosaminide N-acetyltransferase, is an integral lysosomal membrane enzyme. It plays a crucial role in the degradation of heparan sulfate (HS) in the lysosome. Before HS can be degraded by glycosidases, Hgsnat acetylates the terminal glucosamine of HS, using the acetyl group from cytosolic acetyl-CoA in a unique transmembrane acetylation reaction [1,2,4,5,6]. Mutations in Hgsnat lead to HS accumulation, causing mucopolysaccharidosis IIIC, a lysosomal storage disease with progressive neurological deterioration and early death [1,5].
A novel HgsnatP304L mouse model, expressing misfolded HGSNAT Pro304Leu variant, presented earlier deficits in short-term and working/spatial memory compared to constitutive knockout Hgsnat-Geo mice. These mice also showed augmented neuroimmune response, synaptic deficits, and neuronal storage issues. Oral administration of glucosamine rescued memory deficits and most of the brain pathology, suggesting a potential chaperone therapy for patients with misfolded enzyme-causing mutations [3].
In conclusion, Hgsnat is essential for the proper degradation of HS in the lysosome. Mouse models like HgsnatP304L and Hgsnat-Geo have been valuable in revealing the role of Hgsnat in CNS-related pathologies, highlighting its importance in understanding and potentially treating mucopolysaccharidosis IIIC.
References:
1. Zhao, Boyang, Cao, Zhongzheng, Zheng, Yi, Van Lookeren Campagne, Menno, Li, Fei. 2024. Structural and mechanistic insights into a lysosomal membrane enzyme HGSNAT involved in Sanfilippo syndrome. In Nature communications, 15, 5388. doi:10.1038/s41467-024-49614-1. https://pubmed.ncbi.nlm.nih.gov/38918376/
2. Xu, Ruisheng, Ning, Yingjie, Ren, Fandong, Ge, Jingpeng, Yu, Jie. 2024. Structure and mechanism of lysosome transmembrane acetylation by HGSNAT. In Nature structural & molecular biology, 31, 1502-1508. doi:10.1038/s41594-024-01315-5. https://pubmed.ncbi.nlm.nih.gov/38769387/
3. Pan, Xuefang, Taherzadeh, Mahsa, Bose, Poulomee, Morales, Carlos R, Pshezhetsky, Alexey V. 2022. Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT. In The Journal of experimental medicine, 219, . doi:10.1084/jem.20211860. https://pubmed.ncbi.nlm.nih.gov/35704026/
4. Nagel, Lauren, Oliveira, Regiana, Pshezhetsky, Alexey V, Morales, Carlos R. 2019. HGSNAT enzyme deficiency results in accumulation of heparan sulfate in podocytes and basement membranes. In Histology and histopathology, 34, 1377-1385. doi:10.14670/HH-18-131. https://pubmed.ncbi.nlm.nih.gov/31157913/
5. Feldhammer, Matthew, Durand, Stéphanie, Mrázová, Lenka, Kmoch, Stanislav, Pshezhetsky, Alexey V. . Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene. In Human mutation, 30, 918-25. doi:10.1002/humu.20986. https://pubmed.ncbi.nlm.nih.gov/19479962/
6. Navratna, Vikas, Kumar, Arvind, Rana, Jaimin K, Mosalaganti, Shyamal. 2024. Structure of the human heparan-α-glucosaminide N-acetyltransferase (HGSNAT). In eLife, 13, . doi:10.7554/eLife.93510. https://pubmed.ncbi.nlm.nih.gov/39196614/
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