Neurokinin-1 Receptor Knock-Out Mouse
Inventors: Craig Gerard, Norma Gerard
Invention Types: Research Tool
Research Areas: Immunology, Inflammation, Neurology/Neuroscience
Keywords: Animal Model (mouse), Drug ScreeningFor More Information Contact: Khunkhun, Rajinder
Drs. Gerard generated mice deficient in Neurokinin-1 Receptor (NK1R), also know as the substance P receptor, through homologous recombination. NK1R knockout mice demonstrated protection from the secretory and inflammatory changes of toxin A as well as from epithelial cell damage. The protective effect correlated with diminished intestinal levels of TNF-alpha and the leukocyte enzyme myeloperoxidase. The results demonstrated a major requirement for substance P receptor in the pathogenesis of acute inflammatory diarrhea. NK1R -/- mice also show protection against inflammatory disorders (lung immune complex injury) (1), inflammatory oedema in acute interstitial pancreatitis (2) , acute inflammatory diarrhea (3) and impaired endogenous pain control mechanisms (4).
Substance P being involved in orchestrating the physiological and behavioral response to major environmental stressors, mice genetically deficient in NK1R represent a critical animal model for screening NK1 antagonists which may be lead to therapeutics for depression, anxiety, migraine, nociception, acute and chronic inflammation.
NK1R -/- mice represent a critical animal model for screening NK1 antagonists. It is foreseen that a better understanding of the implication of the NK1R in the pathogenesis of acute inflammatory disorders and pain control processes would benefit the worldwide population.
Key Publications: Science. 273(5282):1722-5, 1996; |Br J Pharmacol, 2000. 130(3): p. 505-12; |Clinical Investigation. 101(8):1547-50, 1998; |J Neurosci. 21(3):1039-46, 2001.
IPStatus: None filed