B6.129-Ptp4a3^tm1Geh/J

Stock number: 021159
Research areas: Cancer Research, Research Tools

Description

These mice carry a floxed allele of the Ptp4a3 (protein tyrosine phosphatase 4a3) gene which is is highly expressed in many human cancers. Excision of the floxed region with Cre recombinase results in a null allele.

Detailed description

Ptp4a3 (protein tyrosine phosphatase 4a3) is a prenylated/lipidated protein tyrosine phosphatase that is highly expressed in many human cancers (including tumors of the colon, breast, ovary, liver, stomach, and stroma). It is correlated with tumor metastasis and poor patient prognosis, but is not well characterized.

These mice carry a floxed allele of the gene. Exon 2, encoding the transcriptional start site of the gene, is flanked by loxP sites. Excision of the floxed region with Cre recombinase results in a null allele, as determined by Western blot analysis.

Global homozygous null mice were generated from crosses with a transgenic EIIa-Cre strain (e.g. see Stock No. 003724). Cre was subsequently bred out of the knockout model. Mice deficient for functional Ptp4a3 are grossly and histologically normal, but fewer null males are reportedly observed at weaning age and they maintain a slightly (10%) decreased body mass and body mass index (BMI). This phenotype is not observed in female offspring of the same mice.

In a model of murine colitis-associated colon cancer, male Ptp4a3-null mice exposed to azoxymethane and dextran sodium sulfate (AOM/DSS) develop 50% fewer colon tumors than wildtype mice 16 weeks after initial treatment. Tumors from wildtype and Ptp4a3-null mice do not significantly differ in size during the 12-16 week post-treatment period (average diameter 3-4 mm). Loss of Ptp4a3 increases IGF1RB (Igfr1, insulin-like growth factor I receptor) and c-Myc (Myc, myelocytomatosis oncogene) protein expression in tumors compared to wildtype.

Development

Exon 2, encoding the transcriptional start site, was flanked by loxP sites in (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. This strain was backcrossed to C57BL/6J for more than 5 generations by the donating laboratory.

Allele

Symbol: Ptp4a3^tm1Geh
Name: targeted mutation 1, Gregg E Homanics
MGI accession ID: MGI:5461469
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Ptp4a3
Marker name: protein tyrosine phosphatase 4a3
Chromosome: 15
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A loxP site was inserted upstream of exon 2. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 2. Flp-mediated recombination removed the neo cassette.