Membrane-Type 4 Matrix Metalloproteinase

• Published in: PloS one Vol. 6; no. 2; p. e17099
• Main Authors: Srichai, Manakan B, Colleta, Heloisa, Gewin, Leslie, Matrisian, Linsey, Abel, Ty W, Koshikawa, Naohiko, Seiki, Motoharu, Pozzi, Ambra, Harris, Raymond C, Zent, Roy
• Format: Journal Article
• Language: English
• Published: Public Library of Science 11.02.2011
• Subjects: Embryonic development; Physiological aspects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017099

MT4-MMP is a membrane-type metalloproteinase (MMP) anchored to the membrane by a glycosyl-phosphatidylinositol (GPI) motif. GPI-type MT-MMPs (MT4- and MT6-MMP) are related to other MT-MMPs, but their physiological substrates and functions in vivo have yet to be identified. In this manuscript we show that MT4-MMP is expressed early in kidney development, as well as in the adult kidney, where the highest levels of expression are found in the papilla. MT4-MMP null mice had minimal renal developmental abnormalities, with a minor branching morphogenesis defect in early embryonic kidney development and slightly dysmorphic collecting ducts in adult mice. Interestingly, MT4-MMP null mice had higher baseline urine osmolarities relative to wild type controls, but these animals were able to concentrate and dilute their urines normally. However, MT4-MMP-null mice had decreased daily water intake and daily urine output, consistent with primary hypodipsia. MT4-MMP was shown to be expressed in areas of the hypothalamus considered important for regulating thirst. Thus, our results show that although MT4-MMP is expressed in the kidney, this metalloproteinase does not play a major role in renal development or function; however it does appear to modify the neural stimuli that modulate thirst.