Abstract
Disabled-2 (Dab2) is a phosphoprotein involved in cellular signal transduction and endocytic trafficking. The expression of Dab2 is frequently lost or suppressed in several epithelial tumors, and studies of its cellular function and growth suppressive activity when re-expressed in cancer cells led to the suggestion that Dab2 is a tumor suppressor. A role for Dab2 in epithelial cell positioning organization was derived from study of knockout mice: homozygous deletion of
dab2
results in early embryonic lethality due to the disorganization of the primitive endoderm, the first epithelium in early embryos. We now report that
dab2
heterozygous mice develop uterine hyperplasia and ovarian preneoplastic morphological changes at a high frequency. Crossing into a
p53
−/−
background unexpectedly produced few female
dab2
+/−
:
p53
−/−
mice, while the male
dab2
+/−
:
p53
−/−
were born at the expected Mendelian frequency. The tumor-prone phenotype of
dab2
+/−
mice provides additional support for a role of human Dab2 as a tumor suppressor, and the sex-biased embryonic lethality suggests a genetic interaction between
p53
and
dab2
genes in female mice.
