Brain Expression of CPB2 and Effects of Cpb2 Deficiency in Mouse Models of Behavior.
| Autor: | Meijers JCM; Department of Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, The Netherlands.; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands.; Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands., van der Harst J; DeltaPhenomics B.V., Schaijk, The Netherlands., Marx PF; Department of Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, The Netherlands., Sahbaie P; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, United States.; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States., Clark DJ; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, United States.; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States., Morser J; Division of Hematology, Stanford University School of Medicine, Stanford, California, United States.; Palo Alto Institute of Research and Education, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Thrombosis and haemostasis [Thromb Haemost] 2024 Jan; Vol. 124 (1), pp. 4-19. Date of Electronic Publication: 2023 Aug 02. |
| DOI: | 10.1055/s-0043-1771304 |
| Abstrakt: | Background: Procarboxypeptidase B2 (proCPB2 or TAFI) is a zymogen that after activation cleaves C-terminal basic residues from peptides or proteins with many identified targets. A splice variant of CPB2 has been found in the brain lacking essential residues for its carboxypeptidase function. The aim was to determine CPB2 expression in the brain and effects of CPB2 deficiency ( Cpb2 -/- ) on behavior. Materials and Methods: Behavioral effects were tested by comparing Cpb2 -/- mice in short-term (open field and elevated zero maze tests) and long-term (Phenotyper) observations with wild-type (WT) controls. Results: Long-term observation compared day 1 (acclimatizing to novel environment) to day 4 (fully acclimatized) with the inactive (day) and active (night) periods analyzed separately. Brain expression of CPB2 mRNA and protein was interrogated in publicly available databases. Long-term observation demonstrated differences between WT and Cpb2 -/- mice in several parameters. For example, Cpb2 -/- mice moved more frequently on both days 1 and 4, especially in the normally inactive periods. Cpb2 -/- mice spent more time on the shelter and less time in it. Differences were more pronounced on day 4 after the mice had fully acclimatized. In short-term observations, no differences were observed between Cpb2 -/- mice and WT mice. Brain expression of CBP2 was not detectable in the human protein atlas. Databases of single-cell RNAseq did not show expression of CPB2 mRNA in either human or mouse brain. Conclusion: Continuous observation of home-cage behavior suggests that Cpb2 -/- mice are more active than WT mice, show different day-night activity levels, and might have a different way of processing information. Competing Interests: J.v.d.H. was employed at Delta Phenomics B.V., for which she was also involved as Study Director for the reported study. Currently she is employed at Danone Nutricia Research without any direct or indirect relation to the work reported here. The other authors have nothing to disclose. (Thieme. All rights reserved.) |
| Databáze: | MEDLINE |
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