Phenotypic analysis of Meltrin alpha (ADAM12)-deficient mice: involvement of Meltrin alpha in adipogenesis and myogenesis.
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.
Kurisaki
Tomohiro
T
Field of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Japan.
Masuda
Aki
A
Sudo
Katsuko
K
Sakagami
Junko
J
Higashiyama
Shigeki
S
Matsuda
Yoichi
Y
Nagabukuro
Akira
A
Tsuji
Atsushi
A
Nabeshima
Yoichi
Y
Asano
Masahide
M
Iwakura
Yoichiro
Y
Sehara-Fujisawa
Atsuko
A
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
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