Altered NPY and AgRP in membrane type-1 matrix metalloproteinase-deficient mice

Membrane-type-I matrix metalloproteinase (MTI-MMP) knockout (KO) mice fail to gain weight and die 3-4 weeks after birth. To understand the wasting phenotype in MTI-MMP-KO mice we studied the expression of some hypothalamic neuropeptides involved in control of appetite and body weight. In MTI-MMP-KO mice, neuronal perikarya in the arcuate nucleus displayed accumulations of NPY and agouti-related protein (AgRP) immunoreactivity (-ir). In contrast, NPY-ir and AgRP-ir were reduced in the projection areas of the arcuate neurons. NPY and AgRP are known to relay metabolic signals from the periphery into the brain to stimulate body weight gain. Their altered subcellular distribution suggests that MTI-MMP is involved in postnatal development of the arcuate NPY/AgRP-systenn which may contribute to the generation of the wasting phenotype.