Human IQGAP1 is a widely expressed 190-kDa Cdc42-, Rac1-, and calmodulin-bi
nding protein that interacts with F-actin in vivo and that can cross-link F
-actin microfilaments in vitro. Recent results have implicated IQGAP1 as a
component of pathways via which Cdc42 or Rad modulates cadherin-based cell
adhesion (S, Kuroda et al,, Science 281:832-835, 1998), whereas yeast IQGAP
-related proteins have been found to play essential roles during cytokinesi
s. To identify critical in vivo functions of IQGAP1, we generated deficient
mice by gene targeting. We demonstrate that IQGAP1 null mutants arise at n
ormal frequency and show no obvious defects during development or for most
of their adult life. Loss of IQGAP1 also does not affect tumor development
or tumor progression, but mutant mice exhibit a significant (P < 0.0001) in
crease in late-onset gastric hyperplasia relative to wild-type animals of t
he same genetic background. While we cannot exclude that functional redunda
ncy with IQGAP2 contributes to the Lack of developmental phenotypes, the re
stricted expression pattern of IQGAP2 is not obviously altered in adult IQG
AP1 mutant mice. Thus, IQGAP1 does not serve any essential nonredundant fun
ctions during murine development but may serve to maintain the integrity of
the gastric mucosa in older animals.