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Gene Review

Mme  -  membrane metallo endopeptidase

Mus musculus

Synonyms: 6030454K05Rik, Atriopeptidase, C85356, CALLA, CD10, ...
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Disease relevance of Mme


Psychiatry related information on Mme


High impact information on Mme


Chemical compound and disease context of Mme


Biological context of Mme

  • Because we have previously shown that intestinal inflammation results in down-regulation of NEP and diminished degradation of SP, our present results suggest that defects in NEP expression contribute to uncontrolled inflammation [1].
  • In NEP knockout mice, the SP concentration in the colon was approximately 2.5-fold higher than in wild-type mice, suggesting increased bioavailability of SP [1].
  • The use of NEP antagonists as candidate drugs in cardiovascular disease is suggested by the blood pressure data reported herein [11].
  • Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function [17].
  • Finally, we show that NCT expression peaked 24 h after NCT cDNA transfection of wild-type and NCT-/- fibroblasts, while neprilysin expression drastically increased only after 36 h and was maximal at 48 h [18].

Anatomical context of Mme


Associations of Mme with chemical compounds


Enzymatic interactions of Mme

  • D. melanogaster NEP2 also differs from human NEP in the manner in which the peptidase cleaves the tachykinin, GPSGFYGVR-amide [23].

Regulatory relationships of Mme


Other interactions of Mme

  • However, the mRNAs of PPT-B, PPT-C and NEP appeared in blastocyst-stage embryos [26].
  • We have investigated the use of NEP as a potential therapeutic agent to prevent the accumulation of Abeta peptides in the brain [4].
  • Conversely, genetic deletion of NEP significantly worsened survival (0% vs 90% at 120 hours, P <.001) and exacerbated pancreatic MPO and pancreatitis-associated lung injury [27].
  • We determined whether genetic deletion of the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP increases mortality in a lethal model of hemorrhagic pancreatitis [27].
  • Here, we examined the influence of endogenous nicastrin (NCT), a member of the gamma-secretase complex, on neprilysin physiology [18].

Analytical, diagnostic and therapeutic context of Mme


  1. Neutral endopeptidase (EC terminates colitis by degrading substance P. Sturiale, S., Barbara, G., Qiu, B., Figini, M., Geppetti, P., Gerard, N., Gerard, C., Grady, E.F., Bunnett, N.W., Collins, S.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Neutral endopeptidase terminates substance P-induced inflammation in allergic contact dermatitis. Scholzen, T.E., Steinhoff, M., Bonaccorsi, P., Klein, R., Amadesi, S., Geppetti, P., Lu, B., Gerard, N.P., Olerud, J.E., Luger, T.A., Bunnett, N.W., Grady, E.F., Armstrong, C.A., Ansel, J.C. J. Immunol. (2001) [Pubmed]
  3. Deletion of neutral endopeptidase exacerbates intestinal inflammation induced by Clostridium difficile toxin A. Kirkwood, K.S., Bunnett, N.W., Maa, J., Castagliolo, I., Liu, B., Gerard, N., Zacks, J., Pothoulakis, C., Grady, E.F. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  4. Neprilysin regulates amyloid Beta peptide levels. Marr, R.A., Guan, H., Rockenstein, E., Kindy, M., Gage, F.H., Verma, I., Masliah, E., Hersh, L.B. J. Mol. Neurosci. (2004) [Pubmed]
  5. Neutral endopeptidase and alcohol consumption, experiments in neutral endopeptidase-deficient mice. Siems, W., Maul, B., Krause, W., Gerard, C., Hauser, K.F., Hersh, L.B., Fischer, H.S., Zernig, G., Saria, A. Eur. J. Pharmacol. (2000) [Pubmed]
  6. Alterations within the endogenous opioid system in mice with targeted deletion of the neutral endopeptidase ('enkephalinase') gene. Fischer, H.S., Zernig, G., Schuligoi, R., Miczek, K.A., Hauser, K.F., Gerard, C., Saria, A. Regul. Pept. (2000) [Pubmed]
  7. Effect of inhibition of neuropeptidases on the pain threshold of mice and rats. Carenzi, A., Frigeni, V., Reggiani, A., Della Bella, D. Neuropharmacology (1983) [Pubmed]
  8. Spatial learning in deer mice: sex differences and the effects of endogenous opioids and 60 Hz magnetic fields. Kavaliers, M., Ossenkopp, K.P., Prato, F.S., Innes, D.G., Galea, L.A., Kinsella, D.M., Perrot-Sinal, T.S. J. Comp. Physiol. A (1996) [Pubmed]
  9. Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Lazarov, O., Robinson, J., Tang, Y.P., Hairston, I.S., Korade-Mirnics, Z., Lee, V.M., Hersh, L.B., Sapolsky, R.M., Mirnics, K., Sisodia, S.S. Cell (2005) [Pubmed]
  10. Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation. Saito, T., Iwata, N., Tsubuki, S., Takaki, Y., Takano, J., Huang, S.M., Suemoto, T., Higuchi, M., Saido, T.C. Nat. Med. (2005) [Pubmed]
  11. The control of microvascular permeability and blood pressure by neutral endopeptidase. Lu, B., Figini, M., Emanueli, C., Geppetti, P., Grady, E.F., Gerard, N.P., Ansell, J., Payan, D.G., Gerard, C., Bunnett, N. Nat. Med. (1997) [Pubmed]
  12. The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice. Roques, B.P., Fournié-Zaluski, M.C., Soroca, E., Lecomte, J.M., Malfroy, B., Llorens, C., Schwartz, J.C. Nature (1980) [Pubmed]
  13. Neutral endopeptidase knockout induces hyperalgesia in a model of visceral pain, an effect related to bradykinin and nitric oxide. Fischer, H.S., Zernig, G., Hauser, K.F., Gerard, C., Hersh, L.B., Saria, A. J. Mol. Neurosci. (2002) [Pubmed]
  14. Mixed inhibitors of angiotensin-converting enzyme (EC and enkephalinase (EC rational design, properties, and potential cardiovascular applications of glycopril and alatriopril. Gros, C., Noël, N., Souque, A., Schwartz, J.C., Danvy, D., Plaquevent, J.C., Duhamel, L., Duhamel, P., Lecomte, J.M., Bralet, J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  15. Tumor-suppressive effects of neutral endopeptidase in androgen-independent prostate cancer cells. Dai, J., Shen, R., Sumitomo, M., Goldberg, J.S., Geng, Y., Navarro, D., Xu, S., Koutcher, J.A., Garzotto, M., Powell, C.T., Nanus, D.M. Clin. Cancer Res. (2001) [Pubmed]
  16. Genetic susceptibility of mice to Candida albicans vaginitis correlates with host estrogen sensitivity. Clemons, K.V., Spearow, J.L., Parmar, R., Espiritu, M., Stevens, D.A. Infect. Immun. (2004) [Pubmed]
  17. Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function. Huang, S.M., Mouri, A., Kokubo, H., Nakajima, R., Suemoto, T., Higuchi, M., Staufenbiel, M., Noda, Y., Yamaguchi, H., Nabeshima, T., Saido, T.C., Iwata, N. J. Biol. Chem. (2006) [Pubmed]
  18. Neprilysin activity and expression are controlled by nicastrin. Pardossi-Piquard, R., Dunys, J., Yu, G., St George-Hyslop, P., Alves da Costa, C., Checler, F. J. Neurochem. (2006) [Pubmed]
  19. A role for mesenchyme-derived tachykinins in tooth and mammary gland morphogenesis. Weil, M., Itin, A., Keshet, E. Development (1995) [Pubmed]
  20. Functional and molecular characterization of tachykinins and tachykinin receptors in the mouse uterus. Patak, E., Pinto, F.M., Story, M.E., Pintado, C.O., Fleming, A., Page, N.M., Pennefather, J.N., Candenas, M.L. Biol. Reprod. (2005) [Pubmed]
  21. Neurogenic plasma leakage in mouse airways. Baluk, P., Thurston, G., Murphy, T.J., Bunnett, N.W., McDonald, D.M. Br. J. Pharmacol. (1999) [Pubmed]
  22. Thiorphan, a neutral endopeptidase inhibitor used for diarrhoea, is neuroprotective in newborn mice. Medja, F., Leli??vre, V., Fontaine, R.H., Lebas, F., Leroux, P., Ouimet, T., Saria, A., Rougeot, C., Dournaud, P., Gressens, P. Brain (2006) [Pubmed]
  23. Drosophila melanogaster NEP2 is a new soluble member of the neprilysin family of endopeptidases with implications for reproduction and renal function. Thomas, J.E., Rylett, C.M., Carhan, A., Bland, N.D., Bingham, R.J., Shirras, A.D., Turner, A.J., Isaac, R.E. Biochem. J. (2005) [Pubmed]
  24. Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease. Jelicks, L.A., Chandra, M., Shirani, J., Shtutin, V., Tang, B., Christ, G.J., Factor, S.M., Wittner, M., Huang, H., Weiss, L.M., Mukherjee, S., Bouzahzah, B., Petkova, S.B., Teixeira, M.M., Douglas, S.A., Loredo, M.L., D'Orleans-Juste, P., Tanowitz, H.B. Int. J. Parasitol. (2002) [Pubmed]
  25. Composite effects of actinonin when inhibiting enkephalin-degrading enzymes. Hachisu, M., Hiranuma, T., Shibazaki, Y., Uotani, K., Murata, S., Aoyagi, T., Umezawa, H. Eur. J. Pharmacol. (1987) [Pubmed]
  26. A role for tachykinins in female mouse and rat reproductive function. Pintado, C.O., Pinto, F.M., Pennefather, J.N., Hidalgo, A., Baamonde, A., Sanchez, T., Candenas, M.L. Biol. Reprod. (2003) [Pubmed]
  27. Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice. Maa, J., Grady, E.F., Yoshimi, S.K., Drasin, T.E., Kim, E.H., Hutter, M.M., Bunnett, N.W., Kirkwood, K.S. Surgery (2000) [Pubmed]
  28. Role of abnormal neutral endopeptidase-like activities in Hyp mouse bone cells in renal phosphate transport. Dubois, S.G., Ruchon, A.F., Delalandre, A., Boileau, G., Lajeunesse, D. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  29. Targeted deletion of the neutral endopeptidase gene alters ventilatory responses to acute hypoxia in mice. Grasemann, H., Lu, B., Jiao, A., Boudreau, J., Gerard, N.P., De Sanctis, G.T. J. Appl. Physiol. (1999) [Pubmed]
  30. Neutral endopeptidase determines the severity of pancreatitis-associated lung injury. Day, A.L., Wick, E., Jordan, T.H., Jaffray, C.E., Bunnett, N.W., Grady, E.F., Kirkwood, K.S. J. Surg. Res. (2005) [Pubmed]
  31. The distribution of CD10 (NEP 24.11, CALLA) in humans and mice is similar in non-lymphoid organs but differs within the hematopoietic system: absence on murine T and B lymphoid progenitors. Kalled, S.L., Siva, N., Stein, H., Reinherz, E.L. Eur. J. Immunol. (1995) [Pubmed]
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