A Novel, Secreted Form of Human ADAM 12 (Meltrin α) Provokes Myogenesis in Vivo*
- Brent J. Gilpin‡,
- Frosty Loechel‡,
- Marie-Geneviève Mattei§,
- Eva Engvall¶,
- Reidar Albrechtsen‡ and
- Ulla M. Wewer‡‖
- From the ‡Institute of Molecular Pathology, University of Copenhagen, Copenhagen, 2100 Denmark, the§Faculté de Médicine de la Timone, Marseille, 13385 France, and the ¶Burnham Institute, La Jolla, California 92037
Abstract
The ADAM (A DisintegrinAnd Metalloprotease) family of cell-surface proteins may have an important role in cellular interactions and in modulating cellular responses. In this report we describe a novel, secreted form of human ADAM 12 (meltrin α), designated ADAM 12-S (S for short), and a larger, membrane-bound form designated ADAM 12-L (L for long form). These two forms arise by alternative splicing of a single gene located on chromosome 10q26. Northern blotting demonstrated that mRNAs of both forms are abundant in human term placenta and are also present in some tumor cell lines. The ADAM 12-L transcript can also be detected in normal human adult skeletal, cardiac, and smooth muscle. Human A204 embryonal rhabdomyosarcoma cells that do not differentiate into muscle cells and do not express any form of ADAM 12 were stably transfected with an ADAM 12-S minigene encoding the disintegrin domain, the cysteine-rich domain, and the unique 34 amino acid carboxyl terminus. Nude mouse tumors derived from these transfected cells contained ectopic muscle cells of apparent mouse origin as shown by species-specific markers. These results may have potential applications in the development of muscle-directed gene and cell therapies.
Footnotes
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↵* This work was supported in part by grants from the Danish Cancer Society and the Danish Medical Research Council (to U. M. W. and R. A.). Our laboratories were also supported by the VELUX, Novo-Nordisk, Munksholm, Haensch, Thaysen, Wærum, Bojesen, Beckett, Hartmann, and Meyer Foundations (to U. M. W. and R. A.) and by the National Institutes of Health (to E. E.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF023476 and AF023477.
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↵‖ To whom correspondence should be addressed: the Institute of Molecular Pathology, University of Copenhagen, Frederik V’s vej 11, DK-2100, Copenhagen, Denmark. Tel.: 45 3532 6056; Fax: 45 3532 6081; E-mail: molera{at}inet.uni-c.dk.
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↵1 The abbreviations used are: ADAM(s), a disintegrin and metalloprotease; aa, amino acid(s); bp, base pair(s); EST, expressed sequence tag; DMEM, Dulbecco’s modified Eagle’s medium; kb, kilobase pair(s); mAb, monoclonal antibody; nt, nucleotides(s); PBS, phosphate-buffered saline; PCR, polymerase chain reaction; RT, reverse transcriptase; SVMPs, snake venom metalloproteases.
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↵2 F. Loechel and U. M. Wewer, manuscript in preparation.
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↵3 Blast server, www.ncbi.nlm.nih.gov.
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↵4 M. E. Durkin and U. M. Wewer, manuscript in preparation.
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↵5 On-line address:www.ncbi.nlm.nih.gov/science96/
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↵6 R. Albrechtsen and U. M. Wewer, unpublished observations.
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- Received September 23, 1997.
- Revision received October 27, 1997.
- The American Society for Biochemistry and Molecular Biology, Inc.
