Abstract
The
Ipl
(
Tssc3
) gene lies in an extended imprinted region of distal mouse chromosome 7, which also contains the
Igf2
gene. Expression of
Ipl
is highest in placenta and yolk sac, where its mRNA is derived almost entirely from the maternal allele.
Ipl
encodes a small cytoplasmic protein with a pleckstrin-homology (PH) domain. We constructed two lines of mice with germ-line deletions of this gene (
Ipl
neo
and
Ipl
loxP
) and another line deleted for the similar but nonimprinted gene
Tih1
. All three lines were viable. There was consistent overgrowth of the Ipl-null placentas, with expansion of the spongiotrophoblast. These larger placentas did not confer a fetal growth advantage; fetal size was normal in Ipl nulls with the
Ipl
neo
allele and was decreased slightly in nulls with the
Ipl
loxP
allele. When bred into an
Igf2
mutant background, the
Ipl
deletion partially rescued the placental but not fetal growth deficiency. Neither fetal nor placental growth was affected by deletion of
Tih1
. These results show a nonredundant function for
Ipl
in restraining placental growth. The data further indicate that
Ipl
can act, at least in part, independently of insulin-like growth factor-2 signaling. Thus, genomic imprinting regulates multiple pathways to control placental size.