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Generation and Characterization of PRL‐3 Knockout Mice
Author(s) -
Zimmerman Mark W.,
Homanics Gregg E.,
Lazo John S.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.772.3
Subject(s) - cre recombinase , knockout mouse , biology , conditional gene knockout , protein tyrosine phosphatase , gene product , gene knockout , phenotype , cancer research , transfection , gene , endocrinology , microbiology and biotechnology , signal transduction , genetics , gene expression , transgene , genetically modified mouse
The Phosphatase of Regenerating Liver‐3 (PRL‐3), along with its family members PRL‐1 and PRL‐2, are small, prenylated, protein tyrosine phosphatases with more than 75% amino acid identity. PRL‐3 was discovered to be overexpressed in metastases derived from colorectal cancer, and further studies have revealed that PRLs may enhance cell migration and invasion. High levels of PRL‐3 expression also correlate with poor prognostic outcome in patients with cancers of the liver, ovary, breast, and pancreas. Despite significant information implicating PRL‐3 as a novel target for the treatment of malignant disease, the substrates and downstream targets of PRL‐3 remain unclear. In order to further elucidate the biology of PRL‐3, as well as its potential roles in cancer and metastasis, we have created a conditional knockout mouse model for PRL‐3 ablation. In our gene‐targeted model, Cre recombinase activity is predicted to result in a functionally inactive gene product with no homology to the wildtype protein. To model the effect of PRL‐3 ablation on a cellular level mouse embryonic fibroblasts possessing the PRL‐3 +/flox and PRL‐3 flox/flox alleles will be transfected with Cre recombinase. Current studies are also aimed at characterizing the phenotypic effect of heterozygous and homozygous knockout in the whole animal as well as dissecting the cellular signaling pathways affected by PRL‐3 knockout.