Thimet oligopeptidase (ec 3.4.24.15) key functions suggested by knockout mice phenotype characterization
Biomolecules
; 9(8): 382, 2019.
Article
in English
| Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP
| ID: but-ib17201
Responsible library:
BR78.1
Localization: BR78.1
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.
Full text:
Available
Collection:
National databases
/
Brazil
Database:
Sec. Est. Saúde SP
/
SESSP-IBPROD
Language:
English
Journal:
Biomolecules
Year:
2019
Document type:
Article