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Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization.
- Source :
- Biomolecules (2218-273X); Aug2019, Vol. 9 Issue 8, p382-382, 1p
- Publication Year :
- 2019
-
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<superscript>−/−</superscript>) 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<superscript>-/-</superscript> 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<superscript>-/-</superscript> and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1<superscript>-/-</superscript> mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1<superscript>-/-</superscript> 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<superscript>-/-</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2218273X
- Volume :
- 9
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Biomolecules (2218-273X)
- Publication Type :
- Academic Journal
- Accession number :
- 138319499
- Full Text :
- https://doi.org/10.3390/biom9080382