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(American Journal of Pathology. 2003;162:321-328.)
© 2003 American Society for Investigative Pathology

Animal Model

Tissue-Specific Inactivation of Murine M6P/IGF2R

Andrew A. Wylie^*, David J. Pulford^*, Alison J. McVie-Wylie, Robert A. Waterland^*, Heather K. Evans^*, Yuan-Tsong Chen, Catherine M. Nolan^*, Terry C. Orton and Randy L. Jirtle^*

From the Departments of Radiation Oncology and Pathology,^* Duke University Medical Center, Durham, North Carolina; the Department of Medical Genetics, Duke University Medical Center, Durham, North Carolina; the Department of Zoology, University College Dublin, Belfield, Ireland; and Safety Assessment, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, United Kingdom

The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and T cell- mediated immunity. M6P/IGF2R is an imprinted gene in mice with expression only from the maternal allele. Complete knockout of this gene causes neonatal lethality, thus preventing analysis of its multifunctional role postnatally. To help elucidate the biological functions of M6P/IGF2R in adulthood, we generated both complete and tissue-specific M6P/IGF2R knockout mice using the Cre/loxP system. We confirm that complete M6P/IGF2R knockout results in fetal overgrowth and neonatal lethality. In contrast, tissue-specific inactivation of this gene in either the liver or skeletal and cardiac muscle gives rise to viable animals with no obvious phenotype. The successful creation of viable tissue-specific M6P/IGF2R knockout mouse models will now allow for detailed analysis of receptor function in a number of cellular processes including brain development, carcinogenesis, lysosomal trafficking, and T cell-mediated immunity.

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