title: Phenotypic analysis of Meltrin alpha (ADAM12)-deficient mice: involvement of Meltrin alpha in adipogenesis and myogenesis.
abstract: Meltrin alpha (ADAM12) is a metalloprotease-disintegrin whose specific expression patterns during development suggest that it is involved in myogenesis and the development of other organs. To determine the roles Meltrin alpha plays in vivo, we generated Meltrin alpha-deficient mice by gene targeting. Although the number of homozygous embryos are close to the expected Mendelian ratio at embryonic days 17 to 18, ca. 30% of the null pups born die before weaning, mostly within 1 week of birth. The viable homozygous mutants appear normal and are fertile. Most of the muscles in the homozygous mutants appear normal, and regeneration in experimentally damaged skeletal muscle is unimpeded. In some Meltrin alpha-deficient pups, the interscapular brown adipose tissue is reduced, although the penetrance of this phenotype is low. Impaired formation of the neck and interscapular muscles is also seen in some homozygotes. These observations suggest Meltrin alpha may be involved in regulating adipogenesis and myogenesis through a linked developmental pathway. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a candidate substrate of Meltrin alpha, and we found that TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ectodomain shedding of HB-EGF is markedly reduced in embryonic fibroblasts prepared from Meltrin alpha-deficient mice. We also report here the chromosomal locations of Meltrin alpha in the mouse and rat.
authors.affiliation: Field of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurisaki
authors.forename: Aki
authors.initials: A
authors.lastname: Masuda
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Junko
authors.initials: J
authors.lastname: Sakagami
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Akira
authors.initials: A
authors.lastname: Nagabukuro
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tsuji
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nabeshima
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sehara-Fujisawa
mesh_terms: D051722:ADAM Proteins; D000072199:ADAM12 Protein; D000273:Adipose Tissue / Q000196:embryology / Q000473:pathology* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002874:Chromosome Mapping; D004622:Embryo, Mammalian / Q000166:cytology; D004815:Epidermal Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D012038:Regeneration / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D004815:Epidermal Growth Factor; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C096115:Adam12 protein, mouse; D013755:Tetradecanoylphorbol Acetate