Thimet oligopeptidase (ec 220.127.116.11) key functions suggested by knockout mice phenotype characterization
Santos, Nilton B. dos; Franco, Roseane D.; Camarini, Rosana; Munhoz, Carolina D.; Eichler, Rosangela A. S.; Gewehr, Mayara C. F.; Reckziege, Patricia; Llanos, Ricardo P.; Dale, Camila S.; Silva, Victoria R. O. da; Borges, Vanessa F.; Lima, Braulio H. F.; Cunha, Fernando Q.; Visniauskas, Bruna; Chagas, Jair R.; Tufik, Sergio; Peres, Fernanda F.; Abilio, Vanessa C.; Florio, Jorge C.; Iwai, Leo Kei ; Rioli, Vanessa ; Prezoto, Benedito Carlos ; Guimaraes, Alessander O.; Pesquero, Joao B.; Bader, Michael; Castro, Leandro M.; Ferro, Emer S.
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.
THOP1; neurodegeneration; inflammation; sepsis; MHC-I; peptidome
Santos NB., Franco RD., Camarini R, Munhoz CD., Eichler RA.S., Gewehr MC.F., et al. Thimet oligopeptidase (ec 18.104.22.168) key functions suggested by knockout mice phenotype characterization. Biomolecules. 2019 Aug;9(8):382. doi:10.3390/biom9080382.
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