Mice lacking the metalloprotease-disintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life Journal Article
| Authors: | Weskamp, G.; Cai, H.; Brodie, T. A.; Higashyama, S.; Manova, K.; Ludwig, T.; Blobel, C. P. |
| Article Title: | Mice lacking the metalloprotease-disintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life |
| Abstract: | MDC9 (ADAM9/meltrin γ) is a widely expressed and catalytically active metalloprotease-disintegrin protein that has been implicated in the ectodomain cleavage of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and as an α secretase for the amyloid precursor protein. In this study, we evaluated the expression of MDC9 during development and generated mice lacking MDC9 (mdc9-/- mice) to learn more about the function of this protein during development and in adults. During mouse development, MDC9 mRNA is ubiquitously expressed, with particularly high expression levels in the developing mesenchyme, heart and brain. Despite the ubiquitous expression of MDC9, mdc9-/- mice appear to develop normally, are viable and fertile, and do not have any major pathological phenotypes compared to wild-type mice. Constitutive and stimulated ectodomain shedding of HB-EGF is comparable in embryonic fibroblasts isolated from mdc9-/- and wild-type mice, arguing against an essential role of MDC9 in HB-EGF shedding in these cells. Furthermore, there were no differences in the production of the APP α and γ secretase cleavage product (p3) and of β- and γ-secretase cleavage product (Aβ) in cultured hippocampal neurons from mdc9-/- or wild-type mice, arguing against an essential major role of MDC9 as an α-secretase in mice. Further studies, including functional challenges and an evaluation of potential compensation by, or redundancy with, other members of the ADAM family or perhaps even with other molecules will be necessary to uncover physiologically relevant functions for MDC9 in mice. |
| Keywords: | epidermal growth factor; controlled study; protein expression; unclassified drug; nonhuman; protein domain; protein function; animal cell; mouse; phenotype; animals; mice; cell viability; embryo; mice, mutant strains; protein binding; membrane proteins; gene product; protein interaction; neurons; mice, inbred c57bl; animalia; protein processing, post-translational; tissue distribution; brain; messenger rna; membrane protein; homozygote; fibroblast; catalysis; protein family; nerve cell; heart; mesenchyme; heparin binding epidermal growth factor; metalloproteinase; adam proteins; amyloid precursor protein; amyloid precursor protein secretases; endopeptidases; hippocampus; amyloid beta-protein precursor; alpha secretase; aspartic endopeptidases; disintegrin; disintegrins; metalloendopeptidases; male; female; priority journal; article; protein mdc9 |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 22 |
| Issue: | 5 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2002-03-01 |
| Start Page: | 1537 |
| End Page: | 1544 |
| Language: | English |
| DOI: | 10.1128/mcb.22.5.1537-1544.2002 |
| PUBMED: | 11839819 |
| PROVIDER: | scopus |
| PMCID: | PMC134708 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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161Manova-Todorova
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