B6-hMASP2 Mice

Catalog Number: C001592

Strain Name: C57BL/6NCya-Masp2em1(hMASP2)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

The MASP2 gene encodes MASP-2, a serum serine protease that serves as a key mediator in complement system activation. MASP-2 initiates the lectin pathway by forming complexes with pattern recognition molecules such as mannose-binding lectin (MBL) and ficolins. Upon pathogen recognition by MBL, MASP-2 is activated and subsequently cleaves complement components C4 and C2, leading to the generation of C3 convertase and triggering downstream complement activation. Beyond its role in the complement cascade, MASP-2 also contributes to the coagulation pathway by cleaving prothrombin to generate thrombin, thereby linking innate immunity and hemostasis [1]. Emerging evidence highlights the clinical significance of MASP2 gene polymorphisms, which are associated with altered susceptibility to infectious diseases and immune-related disorders. Reduced plasma levels of MASP-2 have been linked to increased vulnerability to HIV infection, while elevated MASP-2 activity may exacerbate inflammatory responses [2]. Given its pivotal role in immune regulation, MASP-2 has emerged as a promising therapeutic target. Inhibition of MASP-2 is currently under investigation as a potential strategy for treating a range of conditions, including IgA nephropathy (IgAN) [3], atypical hemolytic uremic syndrome (aHUS), and transplant-associated thrombotic microangiopathy (TA-TMA) [4].

The B6-hMASP2 mouse model, generated through precise gene editing technology, features the in situ replacement of part of the endogenous mouse Masp2 gene with the coding sequence (CDS) of human MASP2. Homozygous B6-hMASP2 mice are viable and fertile, providing a robust platform for studying the pathophysiology of autoimmune and infectious diseases. This model also serves as a valuable tool for the development and preclinical evaluation of MASP-2-targeted therapeutics, offering insights into both mechanistic and translational aspects of complement-mediated diseases.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hMASP2 mice. The coding sequence of exon 1 and part of intron 1 was replaced with the “Human MASP2 CDS-rBG pA” cassette.

 

Application

  • MASP2-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of autoimmune and infectious diseases.

 

References

[1]Xu WD, Liu XY, Su LC, Huang AF. Association of MASP2 levels and MASP2 gene polymorphisms with systemic lupus erythematosus. J Cell Mol Med. 2020 Sep;24(18):10432-10443.
[2]Li Z, Wang M, Zhong H, Huang X, Wu X, Zhang X, Wang J, Deng J, Chen M, Chen L, Tan H. Impact of MASP2 gene polymorphism and gene-tea drinking interaction on susceptibility to tuberculosis. Sci Rep. 2021 Mar 22;11(1):6544.
[3]Filippone EJ, Gulati R, Farber JL. Contemporary review of IgA nephropathy. Front Immunol. 2024 Aug 12;15:1436923.
[4]Elhadad S, Redmond D, Huang J, Tan A, Laurence J. MASP2 inhibition by narsoplimab suppresses endotheliopathies characteristic of transplant-associated thrombotic microangiopathy: in vitro and ex vivo evidence. Clin Exp Immunol. 2023 Jul 21;213(2):252-264.