Generation of two modified mouse alleles of the Hic1 tumor suppressor gene

Genesis. 2011 Mar;49(3):142-51. doi: 10.1002/dvg.20719.

Abstract

HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene located on chromosome 17p13.3, a region frequently hypermethylated or deleted in human neoplasias. In mouse, Hic1 is essential for embryonic development and exerts an antitumor role in adult animals. Since Hic1-deficient mice die perinatally, we generated a conditional Hic1 null allele by flanking the Hic1-coding region by loxP sites. When crossed to animals expressing Cre recombinase in a cell-specific manner, the Hic1 conditional mice will provide new insights into the function of Hic1 in developing and mature tissues. Additionally, we used gene targeting to replace sequence-encoding amino acids 186-893 of Hic1 by citrine fluorescent protein cDNA. We demonstrate that the distribution of Hic1-citrine fusion polypeptide corresponds to the expression pattern of wild-type Hic1. Consequently, Hic1-citrine "reporter" mice can be used to monitor the activity of the Hic1 locus using citrine fluorescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • DNA-Binding Proteins / genetics
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Developmental*
  • Gene Targeting
  • Genes, Reporter
  • Genes, Tumor Suppressor*
  • Integrases / genetics
  • Integrases / metabolism
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • Hic1 protein, mouse
  • Kruppel-Like Transcription Factors
  • Transcription Factors
  • Cre recombinase
  • Integrases