MASP2 (mannose-binding protein-associated serine protease 2)gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is proteolytically processed to generate A and B chains that heterodimerize to form the mature protease. MASP-2 shares a common ancestor with the C1s molecules of the classical complement pathway and is therefore very similar. This protease cleaves complement components C2 and C4 in order to generate C3 convertase in the lectin pathway of the complement system. MASP-1 and -2 trigger the activation of the lectin pathway and MASP-3 may be involved in the activation of the alternative pathway of complement. Variant alleles affecting the expression and structure of the proteins have been associated with a variety of infectious and non-infectious diseases, most commonly as disease modifiers. MASPs mediate processes related to coagulation, bradykinin release, and endothelial and platelet activation.
Gene targeting strategy for B-hMASP2 rats. The exons part 5-11 of rat Masp2 gene, including 3’UTR, were replaced by human MASP2 CDS and 3’UTR in B-hMASP2 rats. The promoter and 5’UTR region of the mouse gene are retained. The mouse-derived genome and human CDS are connected through the P2A.
Human MASP2 was exclusively detectable in homozygous B-hMASP2 mice rats and not in wild-type SD rats.
Targeting strategy
Gene targeting strategy for B-hMASP2 rats. The exons part 5-11 of rat Masp2 gene, including 3’UTR, were replaced by human MASP2 CDS and 3’UTR in B-hMASP2 rats. The promoter and 5’UTR region of the mouse gene are retained. The mouse-derived genome and human CDS are connected through the P2A.
Protein expression analysis in serum
Strain specific MASP2 expression analysis in wild-type SD rats and homozygous B-hMASP2 rats by ELISA. Serum was collected from wild-type SD rats (+/+) (male, 7-week-old, n=3) and homozygous B-hMASP2 rats (H/H) (male, 7-week-old, n=3). Expression level of human MASP2 were analyzed by ELISA (anti-human MASP2 ELISA kit: Hycult Biotech, HK326). Human MASP2 was exclusively detectable in homozygous B-hMASP2 rats. Human MASP2 was detected in human plasma. Values are expressed as mean ± SEM.