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 |
ID |
705557 |
Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6jm2v34 |