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Systems genetics in the rat HXB/BXH family identifies Tti2 as a pleiotropic quantitative trait gene for adult hippocampal neurogenesis and serum glucose
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SYSNO ASEP 0557065 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Systems genetics in the rat HXB/BXH family identifies Tti2 as a pleiotropic quantitative trait gene for adult hippocampal neurogenesis and serum glucose Author(s) Senko, A. N. (DE)
Overall, R. W. (DE)
Šilhavý, Jan (FGU-C) RID, ORCID
Mlejnek, Petr (FGU-C) RID, ORCID
Malínská, H. (CZ)
Hüttl, M. (CZ)
Marková, I. (CZ)
Fabel, K. S. (DE)
Lu, L. (US)
Stuchlík, Aleš (FGU-C) RID, ORCID
Williams, R. W. (US)
Pravenec, Michal (FGU-C) RID, ORCID
Kempermann, G. (DE)Number of authors 13 Article number e1009638 Source Title PLoS Genetics. - : Public Library of Science - ISSN 1553-7404
Roč. 18, č. 4 (2022)Number of pages 35 s. Language eng - English Country US - United States Keywords spontaneously hypertensive-rats ; triple t complex ; ataxia-telangiectasia ; sphingosine 1-phosphate ; mammalian target ; candidate genes ; nervous-system ; cell-survival ; igf-i ; expression OECD category Genetics and heredity (medical genetics to be 3) R&D Projects GA20-00939S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000780213300003 EID SCOPUS 85128526029 DOI 10.1371/journal.pgen.1009638 Annotation Metabolic and neurological disorders are often comorbid, suggesting that biological pathways which orchestrate peripheral homeostasis and the integrity of the nervous system intersect. The genetic architecture behind these relationships is still poorly described, in part because molecular processes in the human brain are very difficult to study. We thus used a rodent genetic reference population to investigate links between adult hippocampal neurogenesis-a cellular plasticity mechanism important for learning flexibility-and metabolism. We measured adult neurogenesis in the family of 30 HXB/BXH rat recombinant inbred strains, who are characterised by stable differences in metabolism, behaviour, and gene expression levels.Because DNA variants affecting distinct traits segregated into different members of the family, it was possible to determine which of the previously published phenotypes correlated to adult neurogenesis due to shared genomic sequence. We found that expression levels of Tti2-a part of a specialised protein chaperone complex regulating stability of PIKK kinases-were concomitantly influencing adult neurogenesis and serum glucose levels. In human populations hundreds of genomic variants regulate TTI2 expression, potentially affecting brain function and glucose homeostasis. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2023 Electronic address https://doi.org/10.1371/journal.pgen.1009638
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