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Molecular and Cellular Biology, January 2000, p. 697-701, Vol. 20, No. 2
Massachusetts General Hospital Cancer Center
and Harvard Medical School, Charlestown, Massachusetts
02129,1 and USDA Human Nutrition
Research Center on Aging, Tufts University, Boston, Massachusetts
021112
Received 30 September 1999/Accepted 11 October 1999
Human IQGAP1 is a widely expressed 190-kDa Cdc42-, Rac1-, and
calmodulin-binding 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 Rac1
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 cytokinesis. To identify
critical in vivo functions of IQGAP1, we generated deficient mice by
gene targeting. We demonstrate that IQGAP1 null mutants arise at normal
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) increase in late-onset gastric
hyperplasia relative to wild-type animals of the same genetic
background. While we cannot exclude that functional redundancy with
IQGAP2 contributes to the lack of developmental phenotypes, the
restricted expression pattern of IQGAP2 is not obviously altered in adult IQGAP1 mutant mice. Thus, IQGAP1 does not serve any
essential nonredundant functions during murine development but may
serve to maintain the integrity of the gastric mucosa in older animals.
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Gastric Hyperplasia in Mice Lacking the Putative Cdc42
Effector IQGAP1

*
Corresponding author. Mailing address: MGH Cancer
Center, Bldg. 149, 13th St., Boston, MA 02129. Phone: (617) 726-5620. Fax: (617) 724-9648. E-mail:
abernard{at}helix.mgh.harvard.edu.
Present address: Geron Corporation, Menlo Park, CA 94025.
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