Mice lacking the metalloprotease-disintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life
Related Experiment Video
Updated: Oct 2, 2026
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
Gisela Weskamp1, Hui Cai, Thomas A Brodie
1Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Abstract:
MDC9 (ADAM9/meltrin gamma) 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 alpha 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 alpha and gamma secretase cleavage product (p3) and of beta- and gamma-secretase cleavage product (A beta) in cultured hippocampal neurons from mdc9(-/-) or wild-type mice, arguing against an essential major role of MDC9 as an alpha-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.
Insights
Mice lacking MDC9 (ADAM9) developed normally, showing no major defects. This suggests MDC9 is not essential for HB-EGF shedding or amyloid precursor protein processing in mice.
Area of Science:
- Molecular Biology
- Developmental Biology
- Neuroscience
Background:
- MDC9 (ADAM9/meltrin gamma) is a metalloprotease-disintegrin implicated in cleaving HB-EGF and acting as an alpha-secretase for APP.
- Understanding MDC9's role in development and adulthood is crucial due to its broad expression.
Purpose of the Study:
- To investigate the expression pattern of MDC9 during mouse development.
- To determine the physiological functions of MDC9 by generating and analyzing knockout mice (mdc9(-/-)).
Main Methods:
- Quantitative analysis of MDC9 mRNA expression during mouse embryogenesis.
- Generation and phenotypic analysis of mdc9(-/-) mice.
- Assessment of HB-EGF shedding in embryonic fibroblasts and APP processing in hippocampal neurons from knockout and wild-type mice.
Main Results:
- MDC9 mRNA is ubiquitously expressed during development, with high levels in the mesenchyme, heart, and brain.
- mdc9(-/-) mice are viable, fertile, and exhibit no major pathological phenotypes compared to wild-type littermates.
- No significant differences in HB-EGF shedding or APP alpha/beta secretase processing were observed between mdc9(-/-) and wild-type mice.
Conclusions:
- MDC9 is not essential for HB-EGF ectodomain shedding in embryonic fibroblasts or for APP alpha-secretase activity in mouse hippocampal neurons.
- The absence of a major phenotype in mdc9(-/-) mice suggests potential functional redundancy with other ADAM family members or compensatory mechanisms.
- Further investigations involving functional challenges are required to elucidate the specific physiological roles of MDC9 in mice.
