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Regulation of embryonic growth and lysosomal targeting by the imprintedIgf2/Mpr gene

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Abstract

THE receptor for insulin-like growth factor type 2, also known as the cation-independent mannose-6-phosphate receptor (Igf2/Mpr), is a multifunctional receptor thought to play a role in lysosomal targeting, cell growth and signal transduction1–8. Igf2/Mpr has been mapped to the mouse Tme9 locus and shown to be an imprinted gene10, which further suggests a role in embryonic growth regulation. To define the functions of Igf2/Mpr, we have generated mice lacking this gene. We report here that maternal inheritance of an Igf2/Mpr null allele (−/+) as well as homo-zygosity for the inactive allele (−/−) is generally lethal at birth and mutants are about 30% larger, indicating that maternal expression of Igf2/Mpr is essential for late embryonic development and growth regulation. The phenotype is probably caused by an excess of Igf 2 because the introduction of anIgf2 null allele rescued the Igf2/Mpr mutant mice. Mutant mice also have organ and skeletal abnormalities and missort mannose-6-phosphate-tagged proteins. A few (−/+) mice reactivated their paternal Igf2/Mpr allele in some tissues and survived to adults. But no (−/−) mice survived, indicating a role for the reactivated paternal allele in postnatal survival.

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Authors and Affiliations

  1. Research Institute for Molecular Pathology (I.M.P.), Dr Bohr-Gasse 7, A-1030, Vienna, Austria

    Zhao-Qi Wang, Marion R. Fung, Denise P. Barlow & Erwin F. Wagner

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  1. Zhao-Qi Wang
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  2. Marion R. Fung
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  3. Denise P. Barlow
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  4. Erwin F. Wagner
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Wang, ZQ., Fung, M., Barlow, D. et al. Regulation of embryonic growth and lysosomal targeting by the imprintedIgf2/Mpr gene. Nature 372, 464–467 (1994). https://doi.org/10.1038/372464a0

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