C57BL/6JCya-Sptlc1em1flox/Cya
Common Name:
Sptlc1-flox
Product ID:
S-CKO-18101
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Sptlc1-flox
Strain ID
CKOCMP-268656-Sptlc1-B6J-VB
Gene Name
Product ID
S-CKO-18101
Gene Alias
E030036H05; Lcb1; SPT1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
13
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Sptlc1em1flox/Cya mice (Catalog S-CKO-18101) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000021920
NCBI RefSeq
NM_009269
Target Region
Exon 4~5
Size of Effective Region
~1.4 kb
Detailed Document
Overview of Gene Research
Sptlc1, serine palmitoyltransferase, long chain base subunit 1, is a key subunit of serine palmitoyltransferase (SPT). SPT catalyzes the first step in the de novo synthesis of sphingolipids (SLs), a pathway crucial for maintaining cellular membrane integrity, cell signaling, and various biological processes [1,2,3,4,5,6,7,8].
Mutations in Sptlc1 are associated with several neurological disorders. In particular, certain Sptlc1-ALS variants that map to a transmembrane domain and interact with ORMDL proteins (negative regulators of SPT activity) lead to increased SL synthesis and a distinct lipid signature due to impaired ORMDL binding to the holoenzyme complex [1]. C-terminal Sptlc1 variants cause peripheral hereditary sensory and autonomic neuropathy type 1 (HSAN1) as SPT metabolizes L-alanine instead of L-serine, forming 1-deoxysphingolipids (1-deoxySLs) [1]. Limiting L-serine availability in Sptlc1-ALS-expressing cells can shift the SL profile from an ALS-like to an HSAN1-like signature [1]. Also, Sptlc1 mutations are linked to juvenile amyotrophic lateral sclerosis (ALS), often presenting with early age of symptom onset, muscular weakness, atrophy, and other related symptoms [2,3,4]. Some Sptlc1 mutations associated with juvenile ALS may disrupt the normal homeostatic regulation of SPT [5]. In Sptlc1-related disorders, sphingolipidomic analysis shows co-existence of neurotoxic deoxy-sphingolipids with an excess of canonical SPT products [8].
In conclusion, Sptlc1 is essential for sphingolipid synthesis. Studies on Sptlc1-related mutations in the context of neurological disorders, especially ALS and HSAN1, have provided insights into the role of Sptlc1-mediated sphingolipid metabolism in these diseases. Understanding Sptlc1 function through research on its mutations can potentially offer new therapeutic strategies for these neurological conditions.
References:
1. Lone, Museer A, Aaltonen, Mari J, Zidell, Aliza, Shoubridge, Eric A, Hornemann, Thorsten. 2022. SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins. In The Journal of clinical investigation, 132, . doi:10.1172/JCI161908. https://pubmed.ncbi.nlm.nih.gov/35900868/
2. Lone, Museer A, Zeng, Sen, Bourquin, Florence, Zhang, Ruxu, Hornemann, Thorsten. 2023. SPTLC1 p.Leu38Arg, a novel mutation associated with childhood ALS. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1868, 159359. doi:10.1016/j.bbalip.2023.159359. https://pubmed.ncbi.nlm.nih.gov/37348646/
3. Johnson, Janel O, Chia, Ruth, Miller, Danny E, Zollino, Marcella, Zucchi, Elisabetta. . Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis. In JAMA neurology, 78, 1236-1248. doi:10.1001/jamaneurol.2021.2598. https://pubmed.ncbi.nlm.nih.gov/34459874/
4. Wang, Peishan, Wei, Qiao, Li, Hongfu, Wu, Zhi-Ying. 2023. Clinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations. In Chinese medical journal, 136, 176-183. doi:10.1097/CM9.0000000000002495. https://pubmed.ncbi.nlm.nih.gov/36801857/
5. Li, Chunyu, Hou, Yanbing, Wei, Qianqian, Chen, Yongping, Shang, Huifang. 2023. Mutation screening of SPTLC1 and SPTLC2 in amyotrophic lateral sclerosis. In Human genomics, 17, 28. doi:10.1186/s40246-023-00479-3. https://pubmed.ncbi.nlm.nih.gov/36966328/
6. Zhu, Wen-Kai, Xu, Wen-Hao, Wang, Jun, Zhang, Hai-Liang, Ye, Ding-Wei. 2019. Decreased SPTLC1 expression predicts worse outcomes in ccRCC patients. In Journal of cellular biochemistry, 121, 1552-1562. doi:10.1002/jcb.29390. https://pubmed.ncbi.nlm.nih.gov/31512789/
7. Kong, Zhenzhen, Guo, Xinming, Zhao, Zhijian, Liu, Yongda, Duan, Xiaolu. 2019. SPTLC1 inhibits cell growth via modulating Akt/FOXO1 pathway in renal cell carcinoma cells. In Biochemical and biophysical research communications, 520, 1-7. doi:10.1016/j.bbrc.2019.09.073. https://pubmed.ncbi.nlm.nih.gov/31554600/
8. Fiorillo, Chiara, Capodivento, Giovanna, Geroldi, Alessandro, Nobbio, Lucilla, Nolano, Maria. 2022. The SPTLC1 p.S331 mutation bridges sensory neuropathy and motor neuron disease and has implications for treatment. In Neuropathology and applied neurobiology, 48, e12842. doi:10.1111/nan.12842. https://pubmed.ncbi.nlm.nih.gov/35904184/
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