| Title: | Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice |
| Author(s): | Pendas AM; Zhou Z; Cadinanos J; Freije JM; Wang J; Hultenby K; Astudillo A; Wernerson A; Rodriguez F; Tryggvason K; Lopez-Otin C; |
| Address: | "Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain" |
| ISSN/ISBN: | 1061-4036 (Print) 1061-4036 (Linking) |
| Abstract: | "The mouse ortholog of human FACE-1, Zmpste24, is a multispanning membrane protein widely distributed in mammalian tissues and structurally related to Afc1p/ste24p, a yeast metalloproteinase involved in the maturation of fungal pheromones. Disruption of the gene Zmpste24 caused severe growth retardation and premature death in homozygous-null mice. Histopathological analysis of the mutant mice revealed several abnormalities, including dilated cardiomyopathy, muscular dystrophy and lipodystrophy. These alterations are similar to those developed by mice deficient in A-type lamin, a major component of the nuclear lamina, and phenocopy most defects observed in humans with diverse congenital laminopathies. In agreement with this finding, Zmpste24-null mice are defective in the proteolytic processing of prelamin A. This deficiency in prelamin A maturation leads to the generation of abnormalities in nuclear architecture that probably underlie the many phenotypes observed in both mice and humans with mutations in the lamin A gene. These results indicate that prelamin A is a specific substrate for Zmpste24 and demonstrate the usefulness of genetic approaches for identifying the in vivo substrates of proteolytic enzymes" |
| Keywords: | "Adipocytes/metabolism/*pathology Animals Cell Nucleus/pathology Female Humans Lamin Type A Male Membrane Proteins/*deficiency/genetics Metalloendopeptidases/*deficiency/genetics Mice Mice, Inbred C57BL Mice, Knockout Muscles/metabolism/*pathology Myocardi;" |
| Notes: | "MedlinePendas, Alberto M Zhou, Zhongjun Cadinanos, Juan Freije, Jose M P Wang, Jianming Hultenby, Kjell Astudillo, Aurora Wernerson, Annika Rodriguez, Francisco Tryggvason, Karl Lopez-Otin, Carlos eng Research Support, Non-U.S. Gov't 2002/03/30 Nat Genet. 2002 May; 31(1):94-9. doi: 10.1038/ng871. Epub 2002 Apr 1" |
