Cd46-flox Mouse

Cd46, also known as membrane cofactor protein (MCP), is a ubiquitously expressed complement regulatory protein. It serves as a cofactor for serine protease factor I to cleave and inactivate C3b and C4b deposited on host cells, playing a crucial role in preventing complement-mediated "self-attack" [1,3]. Additionally, it is involved in human reproduction, autophagy, modulating T cell activation and effector functions, and is part of the intracellular complement system (complosome) [1]. It is also a receptor for 11 pathogens, earning it the moniker "pathogen magnet" [1].

Mutations in Cd46 predispose to atypical hemolytic uremic syndrome (aHUS) with low penetrance. In a study of a large single family, individuals carrying a rare, heterozygous Cd46 gene splice-site mutation had reduced Cd4 + T cell-intrinsic Cd46 expression. The diseased mutation carriers had lower peripheral regulatory T cell (Treg) frequencies and carried potentially epistatic, private rare variants in other inborn errors of immunity (IEI)-associated proinflammatory genes compared to healthy carriers, suggesting that these factors may contribute to clinically manifest Cd46 haploinsufficiency-associated immune-dysregulation [2].

In conclusion, Cd46 is essential in complement regulation, immune modulation, and pathogen interaction. Its study through genetic models, as in the case of the family-based analysis of Cd46 mutations, helps in understanding its role in diseases like aHUS and immune-dysregulation. This knowledge provides insights into the mechanisms underlying these disease conditions and may guide the development of new therapeutic strategies.