McMahon AP and Bradley A:
The Wnt-1 (int-1) proto-oncogene is required for development of a
large region of the mouse brain.
Cell 1990 Sep 21;62(6):1073-85
ABSTRACT
The Wnt-1 (int-1) proto-oncogene, which encodes a putative signaling
molecule, is expressed exclusively in the developing central nervous
system and adult testes. To examine the role of Wnt-1, we generated
six independent embryonic stem cell lines in which insertion of a
neoR gene by homologous recombination inactivated a Wnt-1 allele.
Germline chimeras were generated from two lines, and progeny from
matings between heterozygous parents were examined. In all day 9.5
fetuses homozygous for mutated Wnt-1 alleles, most of the midbrain
and some rostral metencephalon were absent. The remainder of the
neural tube and all other tissues were normal. In late-gestation
homozygotes, there was virtually no midbrain and no cerebellum,
while the rest of the fetus was normal. Homozygotes are born, but
die within 24 hr. Thus the normal role of Wnt-1 is in determination
or subsequent development of a specific region of the central
nervous system.
