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Thromb Haemost 2024; 124(01): 004-019
DOI: 10.1055/s-0043-1771304
Coagulation and Fibrinolysis

Brain Expression of CPB2 and Effects of Cpb2 Deficiency in Mouse Models of Behavior

Joost C. M. Meijers
1   Department of Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, The Netherlands
2   Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
3   Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands
,
Johanneke van der Harst   *
4   DeltaPhenomics B.V., Schaijk, The Netherlands
,
Pauline F. Marx   **
1   Department of Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, The Netherlands
,
Peyman Sahbaie
5   Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, United States
6   Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
,
David J. Clark 
5   Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, United States
6   Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
,
John Morser 
7   Division of Hematology, Stanford University School of Medicine, Stanford, California, United States
8   Palo Alto Institute of Research and Education, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
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Abstract

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.

Keywords

alternative splicing - anxiety - behavior - brain - carboxypeptidase B2

Authors' Contribution

J.C.M.M. and J.M. designed the study, interpreted the results, and wrote the manuscript. P.F.M. co-designed and executed the Phenotyper study, and critically reviewed the manuscript. J.v.d.H. supported the design and execution of the Phenotyper study, as well as the data interpretation, and partially wrote the manuscript. P.S. and J.D.C. executed the open field tests, interpreted the results, and critically reviewed the manuscript. All authors approved the final version of the manuscript.


* Current address: Danone Nutricia Research, Utrecht, The Netherlands.


** Current address: Marx Translations, Driebergen, The Netherlands.


Supplementary Material



Publication History

Received: 02 March 2023

Accepted: 20 June 2023

Article published online:
02 August 2023

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