Neutral endopeptidase knockout mice
Inventors: Craig Gerard, Norma Gerard, Bao Lu
Invention Types: Research Tool
Research Areas: Cardiovascular/Cardiology, Neurology/Neuroscience, Infectious Disease
Keywords: Animal Model (mouse), Drug ScreeningFor More Information Contact: Khunkhun, Rajinder
Neutral endopeptidase (NEP) is a type II cell surface metallopeptidase that colocalized with peptidergic neurons in the central nervous sytem, along mucosal epithelial surfaces, and in the brush border of the kidney. NEP knock-out mice were created by homologous recombination by Dr. Gerard and colleagues. These animals are exquisitely sensitive to endotoxic shock (>10-fold increased sensitivity to endotoxin relative to wild-type littermates). They exhibit a widespread plasma extravasation and associated hypotension, fail to proteolyze the amyloid b peptide and show an enhanced aggressive behavior and altered locomotor activity.
For degrading a variety of biologically active peptides that initiate inflammatory, cardiovascular and neurogenic response, NEP regulates signaling pathways involved in major pathophysiological processes such as Alzheimer's disease, nociceptive behavior, anxiety, septic shock, hypertension and cancer. Dr. Gerard and colleagues have generated mice that present a unique model for screening neuropeptide antagonists and for understanding the role of NEP in neuropeptide-related pathophysiological processes.
Mice genetically deficient in NEP will be useful for understanding the role of this enzyme in Alzheimer's disease, nociceptive behavior, anxiety, septic shock, hypertension and cancer and for screening neuropeptide antagonists.
Key Publications: Exp Med. (1995), 181(6): 2271-5; |Nat Med, 1997. 3(8): p. 904-7.
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