Literature search services are currently unavailable. During our hosting provider's UPS upgrade we experienced a hardware failure and are currently working to resolve the issue.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

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 ID: 2202907


  • Thomas KR
  • Capecchi MR



Publication Data

August 30, 1990

Associated Grants


Mesh Terms

  • Animals
  • Blastocyst
  • Cell Line
  • Cerebellum
  • Chimera
  • DNA
  • Female
  • Genotype
  • Heterozygote
  • Homozygote
  • Male
  • Mesencephalon
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity
  • Mutation
  • Nucleic Acid Hybridization
  • Proto-Oncogene Proteins
  • Stem Cells
  • Transfection
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins