title: Tissue-specific inactivation of murine M6P/IGF2R.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Wylie
authors.forename: David J
authors.initials: DJ
authors.lastname: Pulford
authors.forename: Alison J
authors.initials: AJ
authors.lastname: McVie-Wylie
authors.forename: Robert A
authors.initials: RA
authors.lastname: Waterland
authors.forename: Heather K
authors.initials: HK
authors.lastname: Evans
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Nolan
authors.forename: Terry C
authors.initials: TC
authors.lastname: Orton
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jirtle
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D005328:Fetal Viability; D018390:Gene Targeting; D005804:Genes, Lethal; D018392:Genomic Imprinting; D006579:Heterozygote; D006984:Hypertrophy / Q000235:genetics* / Q000473:pathology; D019426:Integrases; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D017527:Receptor, IGF Type 2 / Q000172:deficiency* / Q000235:genetics*; D013154:Spleen / Q000378:metabolism; D014764:Viral Proteins
chemical_list: D017527:Receptor, IGF Type 2; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases