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Thimet oligopeptidase (EC key functions suggested by knockout mice phenotype characterization

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Item Type:Article
Title:Thimet oligopeptidase (EC key functions suggested by knockout mice phenotype characterization
Creators Name:Santos, N.B.D. and Franco, R.D. and Camarini, R. and Munhoz, C.D. and Eichler, R.A.S. and Gewehr, M.C.F. and Reckziegel, P. and Llanos, R.P. and Dale, C.S. and da Silva, V.R.O. and Borges, V.F. and Lima, B.H.F. and Cunha, F.Q. and Visniauskas, B. and Chagas, J.R. and Tufik, S. and Peres, F.F. and Abilio, V.C. and Florio, J.C. and Iwai, L.K. and Rioli, V. and Presoto, B.C. and Guimaraes, A.O. and Pesquero, J.B. and Bader, M. and Castro, L.M. and Ferro, E.S.
Abstract:Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1(-/-)) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1(-/-) exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1(-/-) and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1(-/-) mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1(-/-) mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1(-/-) mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation.
Keywords:THOP1, Neurodegeneration, Inflammation, Sepsis, MHC-I, Peptidome, Animals, Mice
Page Range:382
Date:19 August 2019
Official Publication:https://doi.org/10.3390/biom9080382
PubMed:View item in PubMed

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