Generation of a mouse with conditionally activated signaling through the BMP receptor, ALK2

Authors

  • Tomokazu Fukuda,

    1. Molecular Developmental Biology Group, Laboratory of Reproductive and Developmental Toxicology, Research Triangle Park, North Carolina
    2. Hormones and Cancer Group, Laboratory of Molecular Carcinogenesis, Research Triangle Park, North Carolina
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  • Gregory Scott,

    1. Molecular Developmental Biology Group, Laboratory of Reproductive and Developmental Toxicology, Research Triangle Park, North Carolina
    2. Knock Out Core, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
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  • Yoshihiro Komatsu,

    1. Molecular Developmental Biology Group, Laboratory of Reproductive and Developmental Toxicology, Research Triangle Park, North Carolina
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  • Runa Araya,

    1. Yamada Research Unit, RIKEN Brain Science Institute, Saitama, Japan
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  • Masako Kawano,

    1. Laboratory for Cell Culture Development, RIKEN Brain Science Institute, Saitama, Japan
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  • Manas K. Ray,

    1. Molecular Developmental Biology Group, Laboratory of Reproductive and Developmental Toxicology, Research Triangle Park, North Carolina
    2. Knock Out Core, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
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  • Masahisa Yamada,

    1. Yamada Research Unit, RIKEN Brain Science Institute, Saitama, Japan
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  • Yuji Mishina

    Corresponding author
    1. Molecular Developmental Biology Group, Laboratory of Reproductive and Developmental Toxicology, Research Triangle Park, North Carolina
    • LRDT, NIEHS, 111 Alexander Dr., RTP, NC 27709
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  • This article is a US Government work and, as such, is in the public domain in the United States of America

Abstract

BMP signaling plays pleiotropic roles in various tissues. Transgenic mouse lines that overexpress BMP signaling in a tissue-specific manner would be beneficial; however, production of each tissue-specific transgenic mouse line is labor-intensive. Here, using a Cre-loxP system, we generated a conditionally overexpressing mouse line for BMP signaling through the type I receptor ALK2 (alternatively known as AVCRI, ActRI, or ActRIA). By mating this line with Cre-expression mouse lines, Cre-mediated recombination removes an intervening floxed lacZ expression cassette and thereby permits the expression of a constitutively active form of Alk2 (caAlk2) driven by a ubiquitous promoter, CAG. Tissue specificity of Cre recombination was monitored by a bicistronically expressed EGFP following Alk2 cDNA. Increased BMP signaling was confirmed by ectopic phosphorylation of SMAD1/5/8 in the areas where Cre recombination had occurred. The conditional overexpression system described here provides versatility in investigating gene functions in a tissue-specific manner without having to generate independent tissue-specific transgenic lines. genesis 44:159–167, 2006. Published 2006 Wiley-Liss, Inc.

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