title: Altered NPY and AgRP in membrane type-1 matrix metalloproteinase-deficient mice.
abstract: Membrane-type-1 matrix metalloproteinase (MT1-MMP) knockout (KO) mice fail to gain weight and die 3-4 weeks after birth. To understand the wasting phenotype in MT1-MMP-KO mice we studied the expression of some hypothalamic neuropeptides involved in control of appetite and body weight. In MT1-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 MT1-MMP is involved in postnatal development of the arcuate NPY/AgRP-system which may contribute to the generation of the wasting phenotype.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177, Stockholm, Sweden.
authors.forename: Leah C
authors.initials: LC
authors.lastname: Byrne
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Zhou
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.forename: Sergueï O
authors.initials: SO
authors.lastname: Fetissov
mesh_terms: D054369:Agouti-Related Protein; D000818:Animals; D001066:Appetite / Q000235:genetics / Q000502:physiology; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D015342:DNA Probes; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D015342:DNA Probes; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011506:Proteins; D020781:Matrix Metalloproteinase 1