Ty Abel
Faculty Member
Last active: 3/27/2014

Membrane-type 4 matrix metalloproteinase (MT4-MMP) modulates water homeostasis in mice.

Srichai MB, Colleta H, Gewin L, Matrisian L, Abel TW, Koshikawa N, Seiki M, Pozzi A, Harris RC, Zent R
PLoS One. 2011 6 (2): e17099

PMID: 21347258 · PMCID: PMC3037967 · 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.

MeSH Terms (10)

Animals Gene Deletion Gene Expression Regulation, Enzymologic Homeostasis Hypothalamus, Anterior Kidney Medulla Matrix Metalloproteinase 17 Mice Osmolar Concentration Water

Connections (5)

This publication is referenced by other Labnodes entities:

Links