C57BL/6JCya-Mcfd2em1flox/Cya
Common Name:
Mcfd2-flox
Product ID:
S-CKO-04689
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
Price:
Contact for Pricing
Basic Information
Strain Name
Mcfd2-flox
Strain ID
CKOCMP-193813-Mcfd2-B6J-VA
Gene Name
Product ID
S-CKO-04689
Gene Alias
1810021C21Rik; F5f8d; Lman1ip; Sdnsf
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
17
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Mcfd2em1flox/Cya mice (Catalog S-CKO-04689) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000024963
NCBI RefSeq
NM_139295
Target Region
Exon 3
Size of Effective Region
~0.7 kb
Detailed Document
Overview of Gene Research
MCFD2, or multiple coagulation factor deficiency 2, is an EF-hand domain protein. It forms a calcium-dependent heteromeric complex with LMAN1 (also known as ERGIC-53), and this complex functions as a cargo receptor in the endoplasmic reticulum (ER)-to-Golgi transport pathway. This pathway is crucial for the efficient secretion of various glycoproteins, including coagulation factors V (FV) and VIII (FVIII), as well as α1-antitrypsin (AAT) [2,3,4,5]. Genetic mutations in MCFD2 can lead to combined deficiency of FV and FVIII, a rare bleeding disorder [1,2,3,4,5]. Mouse models have been instrumental in studying the function of MCFD2.
In MCFD2-deficient mice, plasma levels of FV and FVIII are reduced, with levels even lower than those in LMAN1-deficient mice [3]. However, in doubly deficient (MCFD2 and LMAN1) mice, FV and FVIII levels match the higher levels seen in LMAN1-deficient mice, suggesting an alternative pathway for FV/FVIII secretion in these mice [3]. All three groups of deficient mice (MCFD2-deficient, LMAN1-deficient, and doubly deficient) also show decreased plasma levels of AAT and comparable AAT accumulation in hepatocyte ER, indicating a role for MCFD2 in efficient ER exit of AAT [3]. RNAi targeting MCFD2 in mice leads to effective inhibition of MCFD2 expression, prolonged APTT, and decreased FVIII activity, suggesting its potential as an anticoagulant approach [1].
In conclusion, MCFD2 is essential for the ER-to-Golgi transport of key glycoproteins like FV, FVIII, and AAT. The study of MCFD2-deficient mouse models has provided valuable insights into the molecular mechanisms underlying combined FV and FVIII deficiency and the regulation of AAT secretion. These findings have implications for understanding bleeding disorders and developing new anticoagulant therapies.
References:
1. Ma, Siqian, Liu, Boyan, Du, Hong, Ji, Shundong, Jiang, Miao. 2024. RNAi targeting LMAN1-MCFD2 complex promotes anticoagulation in mice. In Journal of thrombosis and thrombolysis, 57, 1349-1362. doi:10.1007/s11239-024-03034-6. https://pubmed.ncbi.nlm.nih.gov/39222205/
2. Zhang, Yuan, Liu, Zhigang, Zhang, Bin. . Separate roles of LMAN1 and MCFD2 in ER-to-Golgi trafficking of FV and FVIII. In Blood advances, 7, 1286-1296. doi:10.1182/bloodadvances.2022008788. https://pubmed.ncbi.nlm.nih.gov/36490287/
3. Zhu, Min, Zheng, Chunlei, Wei, Wei, Ginsburg, David, Zhang, Bin. . Analysis of MCFD2- and LMAN1-deficient mice demonstrates distinct functions in vivo. In Blood advances, 2, 1014-1021. doi:10.1182/bloodadvances.2018018317. https://pubmed.ncbi.nlm.nih.gov/29735583/
4. Zhang, Bin. 2009. Recent developments in the understanding of the combined deficiency of FV and FVIII. In British journal of haematology, 145, 15-23. doi:10.1111/j.1365-2141.2008.07559.x. https://pubmed.ncbi.nlm.nih.gov/19183188/
5. Zheng, Chunlei, Zhang, Bin. 2013. Combined deficiency of coagulation factors V and VIII: an update. In Seminars in thrombosis and hemostasis, 39, 613-20. doi:10.1055/s-0033-1349223. https://pubmed.ncbi.nlm.nih.gov/23852824/
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