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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6287
pubmed:dateCreated
1990-10-4
pubmed:abstractText
The int-1 proto-oncogene was first identified as a gene activated in virally induced mouse mammary tumours. Expression studies, however, suggest that the normal function of this gene may be in spermatogenesis and in the development of the central nervous system. Genes sharing sequence similarity with int-1 have been found throughout the animal kingdom. For example, int-1 has 54% amino-acid identity to the Drosophila segment polarity gene wingless (wg). Both the int-1 and wg gene products seem to be secreted proteins, presumably involved in cell-cell signalling. We have now explored the function of int-1 in the mouse by disrupting one of the two int-1 alleles in mouse embryo-derived stem cells using positive-negative selection. This cell line was used to generate a chimaeric mouse that transmitted the mutant allele to its progeny. Mice heterozygous for the int-1 null mutation are normal and fertile, whereas mice homozygous for the mutation may exhibit a range of phenotypes from death before birth to survival with severe ataxia. The latter pathology in mice and humans is often associated with defects in the cerebellum. Examination of int-1-/int-1- mice at several stages of embryogenesis revealed severe abnormalities in the development of the mesencephalon and metencephalon indicating a prominent role for the int-1 protein is in the induction of the mesencephalon and cerebellum.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
346
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
847-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:2202907-Animals, pubmed-meshheading:2202907-Blastocyst, pubmed-meshheading:2202907-Cell Line, pubmed-meshheading:2202907-Cerebellum, pubmed-meshheading:2202907-Chimera, pubmed-meshheading:2202907-DNA, pubmed-meshheading:2202907-Female, pubmed-meshheading:2202907-Genotype, pubmed-meshheading:2202907-Heterozygote, pubmed-meshheading:2202907-Homozygote, pubmed-meshheading:2202907-Male, pubmed-meshheading:2202907-Mesencephalon, pubmed-meshheading:2202907-Mice, pubmed-meshheading:2202907-Mice, Inbred C57BL, pubmed-meshheading:2202907-Motor Activity, pubmed-meshheading:2202907-Mutation, pubmed-meshheading:2202907-Nucleic Acid Hybridization, pubmed-meshheading:2202907-Proto-Oncogene Proteins, pubmed-meshheading:2202907-Stem Cells, pubmed-meshheading:2202907-Transfection, pubmed-meshheading:2202907-Wnt Proteins, pubmed-meshheading:2202907-Wnt1 Protein, pubmed-meshheading:2202907-Zebrafish Proteins
pubmed:year
1990
pubmed:articleTitle
Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development.
pubmed:affiliation
Howard Hughes Medical Institute, Department of Biology and Human Genetics, Salt Lake City, Utah 84112.
pubmed:publicationType
Journal Article