| First Author | Santos NBD | Year | 2019 |
| Journal | Biomolecules | Volume | 9 |
| Issue | 8 | PubMed ID | 31431000 |
| Mgi Jnum | J:290567 | Mgi Id | MGI:6443968 |
| Doi | 10.3390/biom9080382 | Citation | Santos NBD, et al. (2019) Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization. Biomolecules 9(8):382 |
| abstractText | 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. |
