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C57BL/6JCya-Sdhaem1flox/Cya
Common Name:
Sdha-flox
Product ID:
S-CKO-13404
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Sdha-flox
Strain ID
CKOCMP-66945-Sdha-B6J-VA
Gene Name
Sdha
Product ID
S-CKO-13404
Gene Alias
1500032O14Rik; 2310034D06Rik; 4921513A11; FP; SDH2; SDHF
Background
C57BL/6JCya
NCBI ID
66945
Modification
Conditional knockout
Chromosome
13
Phenotype
MGI:1914195
Document
Click here to download >>
Application
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More
Rare Disease Data Center >>
Note
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Sdhaem1flox/Cya mice (Catalog S-CKO-13404) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000022062
NCBI RefSeq
NM_023281
Target Region
Exon 4~6
Size of Effective Region
~3.7 kb
Detailed Document
Click here to download >>
Overview of Gene Research
Sdha, short for succinate dehydrogenase subunit A, is a key component of the succinate dehydrogenase complex. This complex is involved in the tricarboxylic acid (TCA) cycle and mitochondrial respiratory chain, playing a crucial role in cellular energy metabolism [1,2,3,4,5,6,7].

Loss-of-function of the succinate dehydrogenase complex is seen in 20-40% of all KIT/PDGFRA-negative gastrointestinal stromal tumors (GISTs). Among SDH-deficient GISTs, SDHA mutations are the most common (30%), leading to loss of SDHA and SDHB protein expression [1]. SDHA pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type GISTs [2]. In phaeochromocytomas and paragangliomas, SDHA PVs account for up to 2.8% of cases, with tumors often presenting as single ones, commonly in the head and neck or abdomen, and a 25.5% metastasis rate [3]. In hepatocellular carcinoma, downregulation of SDHA/B is observed, promoting cancer proliferation by stabilizing YAP/TAZ [4]. In diabetic cardiomyopathy, CAV1 binds with SDHA, triggering its ubiquitination and degradation, resulting in mitochondrial dysfunction, which can be alleviated by LNT [6]. In primary antibody deficiency, SDHA gain-of-function leads to fumarate accumulation, engaging the KEAP1-Nrf2 system to drive inflammatory cytokine transcription [7].

In conclusion, Sdha is essential for normal cellular energy metabolism. Its dysregulation, as revealed through various disease-related studies rather than KO/CKO mouse models in the provided references, is associated with multiple diseases including GISTs, paraganglioma, phaeochromocytoma, hepatocellular carcinoma, diabetic cardiomyopathy, and primary antibody deficiency. Understanding Sdha's role in these conditions may provide insights for disease management and treatment.

References:
1. Schipani, Angela, Nannini, Margherita, Astolfi, Annalisa, Pantaleo, Maria A. 2023. SDHA Germline Mutations in SDH-Deficient GISTs: A Current Update. In Genes, 14, . doi:10.3390/genes14030646. https://pubmed.ncbi.nlm.nih.gov/36980917/
2. Hanson, Helen, Durkie, Miranda, Lalloo, Fiona, Woodward, Emma Roisin, Maher, Eamonn R. 2022. UK recommendations for SDHA germline genetic testing and surveillance in clinical practice. In Journal of medical genetics, 60, 107-111. doi:10.1136/jmedgenet-2021-108355. https://pubmed.ncbi.nlm.nih.gov/35260474/
3. Kaplan, Adam I, Dwight, Trisha, Luxford, Catherine, Benn, Diana E, Clifton-Bligh, Roderick J. 2024. SDHA-related phaeochromocytoma and paraganglioma: review and clinical management. In Endocrine-related cancer, 31, . doi:10.1530/ERC-24-0111. https://pubmed.ncbi.nlm.nih.gov/39133175/
4. Yuan, Tao, Zhou, Tianyi, Qian, Meijia, Zhu, Hong, Yang, Bo. 2022. SDHA/B reduction promotes hepatocellular carcinoma by facilitating the deNEDDylation of cullin1 and stabilizing YAP/TAZ. In Hepatology (Baltimore, Md.), 78, 103-119. doi:10.1002/hep.32621. https://pubmed.ncbi.nlm.nih.gov/35713976/
5. Bausch, Birke, Schiavi, Francesca, Ni, Ying, Eng, Charis, Neumann, Hartmut P H. . Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention. In JAMA oncology, 3, 1204-1212. doi:10.1001/jamaoncol.2017.0223. https://pubmed.ncbi.nlm.nih.gov/28384794/
6. Hu, Shuiqing, Luo, Jinlan, Guo, Ping, Fang, Qin, Wang, Yan. 2023. Lentinan alleviates diabetic cardiomyopathy by suppressing CAV1/SDHA-regulated mitochondrial dysfunction. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 167, 115645. doi:10.1016/j.biopha.2023.115645. https://pubmed.ncbi.nlm.nih.gov/37804808/
7. Burgener, Anne-Valérie, Bantug, Glenn R, Meyer, Benedikt J, Recher, Mike, Hess, Christoph. 2019. SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2. In Nature immunology, 20, 1311-1321. doi:10.1038/s41590-019-0482-2. https://pubmed.ncbi.nlm.nih.gov/31527833/
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
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