Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development.

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Publication Type Journal Article
School or College College of Science; School of Medicine
Department Internal Medicine; Oncological Sciences; Human Genetics; Biology
Program Institute of Human Genetics; Howard Hughes Medical Institute (HHMI)
Creator Thomas, Kirk R.; Capecchi, Mario R.
Title Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development.
Date 1990-08-30
Description 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.
Type Text
Publisher Nature Publishing Group
Volume 346
Issue 6287
First Page 847
Last Page 850
Subject Animals; Blastocyst; Cell Line; Chimera; DNA; Female; Genotype; Heterozygote; Homozygote; Male; Mice, Inbred C57BL; Motor Activity
Subject MESH Cerebellum; Mesencephalon; Proto-Oncogene Proteins; Zebrafish Proteins
Language eng
Bibliographic Citation Nature. 1990 Aug 30;346(6287):847-50. Thomas KR, Capecchi MR. Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Retrieved on November 2, 2006 from http://www.nature.com/nature/journal/v346/n6287/abs/346847a0.html.
Rights Management copyright © 1990 Nature Publishing Group. All Rights Reserved.
Format Medium application/pdf
Identifier ir-main,568
ARK ark:/87278/s6jm2v34
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 705557
Reference URL https://collections.lib.utah.edu/ark:/87278/s6jm2v34
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