Human membrane cofactor protein (MCP; CD46) is a widely distributed complem
ent regulator. In the mouse, expression of MCP is largely restricted to the
testis while a related, widely expressed protein (Crry) appears to perform
MCP's (CD46) regulatory activity. We have developed two mouse strains tran
sgenic for human MCP (CD46) utilizing an similar to 400 kb YAC clone carryi
ng the complete gene. A third mouse strain was generated using an overlappi
ng YAC clone isolated from a second library. The expression of human MCP (C
D46) in these mouse strains was characterized by immunohistochemistry, FACS
, Western blotting and RT-PCR. No differences were detected in the isoform
pattern or distribution among the three strains, although the expression le
vel varied according to how many copies of the gene were integrated. The ex
pression profile closely mimicked that observed in humans, including the sa
me pattern of isoform expression as the donor. In addition, tissue-specific
isoform expression in the kidney, salivary gland and brain paralleled that
observed in man. The transgenic mice expressed low levels of MCP (CD46) on
their E, in contrast to humans but in line with most other primates. These
mice should be a useful tool to analyse tissue-specific expression, to est
ablish animal models of infections and to characterize the role of MCP (CD4
6) in reproduction.