C.129P2(B6)-Htatip2^tm1Hx/J

Stock number: 018767
Research areas: Apoptosis Research, Cancer Research

Description

These Tip30 KO mice are a useful model for studying tumor suppression.

Detailed description

The coding sequence of the HIV-1 tat interactive protein 2 (Htatip2 or Tip30) gene was replaced with a β-galactosidase (lacZ) sequence and a neomycin resistance (neo) cassette, abolishing gene expression. Tip30 is a metastasis suppressor which promotes apoptosis and inhibits angiogenesis. Deleting Tip30 leads to spontaneous tumors. At 78 weeks of age, 43% of Tip30-/- mice of both sexes developed pulmonary tumors and 22% of Tip30-/- female mice developed mammary tumors. Histopathological analysis revealed that Tip30-/- mice exhibited several types of progressive lesions in the lung, such as atypical adenomatous hyperplasias, adenomas and adenocarcinomas. Homozygous mice are viable and fertile.

Development

A targeting vector was designed to replace the coding sequence, excluding the first 10 codons downstream of translation start site, of the HIV-1 tat interactive protein 2 (Htatip2) gene with a β-galactosidase (lacZ) sequence and a neomycin resistance (neo) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. These Tip30^-/- mice were backcrossed to C57BL/6J mice for at least 10 generations, and subsequently to BALB/c mice for at least 7 generations. Upon arrival at The Jackson Laboratory, mice were bred to BALB/cJ (Stock No. 000651) for at least one generation to establish the colony.

Allele

Symbol: Htatip2^tm1Hx
Name: targeted mutation 1, Hua Xiao
MGI accession ID: MGI:3026855
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Tip30^-
Marker symbol: Htatip2
Marker name: HIV-1 Tat interactive protein 2
Marker synonyms: CC3; SDR44U1; TIP30
Chromosome: 7
Strain of origin: 129P2/OlaHsd
Expressed genes: lacZ,beta-galactosidase,E. coli
Molecular note: A cassette containing lacZ and neo was inserted at the endogenous locus via homologous recombination. The insertion was made 10 codons downstream of the start codon, deleting sequence from 2 exons that encode an N-terminal portion of the exon. Normal transcript was undetected in homozygous mutant mice by Northern blot analysis of RNA obtained from liver and stomach tissue.