B-hFXII mice_Biocytogen Pharmaceuticals (Beijing) Co., Ltd._Biocytogen, drug development, antibody discovery

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동물/세포 모델

동물/세포모델

Humanized Mouse Models

Other Humanized Mice

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B-hFXII mice

Strain Name	C57BL/6N-F12^{tm1(F12)Bcgen}/Bcgen	Common Name	B-hFXII mice
Background	C57BL/6N	Catalog number	112750
Aliases	HAE3, HAEX, HAF
NCBI Gene ID	2161

Description

FXII is a protease that is primarily produced in the liver and circulates as a single-chain zymogen in plasma, playing an important role in the intrinsic pathway of blood coagulation and hemostasis. Upon contact with negatively charged surfaces, FXII converts into its double-stranded active form, FXIIa. The absence of FXII in humans and mice does not affect normal hemostasis ability, and the lack of FXII can inhibit thrombus formation, making it an important target in thrombosis treatment.

Application: This product is used for pharmacodynamics and safety evaluation of cardiovascular diseases such as thrombosis.

Mechanism of action

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Plasmatic coagulation cascade:

Coagulation is triggered by either extrinsic or intrinsic pathways, leading to the generation of thrombin. The extrinsic pathway is initiated during the formation of the TF-FVIIa complex, which activates FX to FXa via FIXa. The intrinsic pathway is initiated by the activation of Factor XII (FXII) mediated by negatively charged surfaces and promotes the generation of thrombin through consecutive activations of FXI, FIX, FX and prothrombin.

Targeting strategy

Gene targeting strategy for B-hFXII mice.
The exons 1~14 of mouse FXII gene that encode full-length protein were replaced by the exons 1~14 of human FXII gene in B-hFXII mice.

Model validation

√: The experiment is planned.
NA: The experiment is not currently planned.
According to the characteristics and applications of the products, you can add experiments in the table by yourself.

mRNA expression analysis in humanized B-hFXII mice

Strain specific analysis of FXII mRNA expression in wild-type C57BL/6N mice and B-hFXII mice by RT-PCR. Liver RNA were isolated from wild-type C57BL/6N mice (+/+) and heterozygous B-hFXII mice (H/+), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human FXII primers. Mouse FXII mRNA were detectable in wild-type C57BL/6N and heterozygous B-hFXII mice. Human FXII mRNA was only detectable in heterozygous B-hFXII mice.

Protein expression analysis in humanized B-hFXII mice

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Strain specific FXII expression analysis in homozygous B-hFXII mice by ELISA. Serum and plasma were collected from wild-type mice C57BL/6N mice (+/+) and homozygous B-hFXII mice (H/H) (n=3), and analyzed by ELISA with species-specific FXII ELISA kit. Mouse FXII was only detectable in wild-type mice (A). Human FXII was exclusively detectable in homozygous mice but not in wild-type mice (B).

Summary

mRNA expression analysis:

Mouse FXII mRNA was detectable in liver of wild-type (+/+) and heterozygous B-hFXII mice (H/+) . Human FXII mRNA was detectable in heterozygous B-hFXII mice (H/+) mice but not in wild-type mice.

Protein expression analysis:

Human FXII was detectable in heterozygous B-hFXII mice (H/+) but not in wild-type mice (+/+).