376 DNA AND CELL BIOLOGY Volume 25, Number 6, 2006 © Mary Ann Liebert, Inc. Pp. 376–382 Genetic Ablation of Ptprj, a Mouse Cancer Susceptibility Gene, Results in Normal Growth and Development and Does Not Predispose to Spontaneous Tumorigenesis FRANCESCO TRAPASSO, 1,2, * ALESSANDRA DRUSCO, 2, * STEFAN COSTINEAN, 2, * HANSJUERG ALDER, 2, * RAMI I. AQEILAN, 2, * RODOLFO IULIANO, 1,2, * EUGENIO GAUDIO, 1 CINZIA RASO, 1 NICOLA ZANESI, 2, * CARLO M. CROCE, 2, * and ALFREDO FUSCO 3,4 ABSTRACT Ptprj is a ubiquitously expressed murine gene encoding a receptor-type protein tyrosine phosphatase, which has recently been proposed as a candidate gene on the locus Scc1 for colon cancer susceptibility. It has been demonstrated that PTPRJ, the human homologue of Ptprj, is involved in the control of cell growth and ad- hesion, being furthermore altered in several types of cancer including mammary, thyroid, lung, colon, and pancreatic cancers. To investigate the biological functions of Ptprj, we have generated mice deficient in this receptor protein tyrosine phosphatase. Ptprj-deficient mice are viable, fertile, and show no gross anatomical alterations. Furthermore, neither changes in life span nor spontaneous tumor appearance were observed in Ptprj-null mice. Our results indicate that Ptprj is dispensable for normal growth and development in mice. INTRODUCTION T HE HUMAN PTPRJ (also known as DEP-1, HPTP, CD148) is a receptor-type protein tyrosine phoshatase of class I (Alonso et al., 2004) that is positively regulated by contact in- hibition in densely cultured fetal lung fibroblasts (Ostman et al., 1994). PTPRJ is a ubiquitous gene; in fact, it is expressed in all the investigated tissues, including brain, liver, spleen, thy- roid, and endothelial cells (Borges et al., 1996; Kuramochi et al., 1996; Zhang et al., 1997). PTPRJ maps at chromosome 11p11.2, a region involved in human tumors through loss of heterozygosity (Honda et al., 1994); its involvement in human and experimental tumorigen- esis is reported by several papers. PTPRJ is able to inhibit the growth of breast cancer cells (Keane et al., 1996). We demon- strated that the expression of the rat homologue of PTPRJ was downregulated in an in vitro model of thyroid tumorigenesis, and that its exogenous reconstitution in rat thyroid malignant cells was able to block their proliferation through the stabi- lization of the cell cycle inhibitor p27 Kip1 (Trapasso et al., 2000). More recently, Ptprj was indicated as a candidate for the mouse colon-cancer susceptibility locus, Scc1. Furthermore, in- activation of human PTPRJ through loss of heterozygosity was demonstrated at a high rate in human specimens of colon, mam- mary, lung, and thyroid tumors (Ruivenkamp et al., 2002, 2003; Iuliano et al., 2004). Finally, the use of PTPRJ as a therapeu- tic gene was successful in preclinical models of human thyroid and pancreatic tumors (Iuliano et al., 2003, Trapasso et al., 2004). A role for PTPRJ was also assessed in vasculogenesis; in fact, its reduced activity in enhanced VEGF-induced VEGFR2 activity leads to increased cellular responses, supporting a PT- PRJ/VEGFR2 interaction (Lampugnani et al., 2003). Further- more, PTPRJ has been implicated in the negative regulation of the platelet-derived growth factor receptor (PDGFR), another modulator of proliferation and migration of vascular smooth 1 Dipartimento di Medicina Sperimentale e Clinica, Università “Magna Græcia” di Catanzaro, Campus Germaneto, Catanzaro, Italy. 2 Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania. 3 Dipartimento di Biologia e Patologia Cellulare e Molecolare, c/o Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Università “Federico II” di Napoli, Naples, Italy. 4 NOGEC (Naples Oncogenomic Center)-CEINGE, Biotecnologie Avanzate, Naples, Italy. *Present address: Ohio State University, Columbus, Ohio.