Systems genetics in the rat HXB/BXH family identifies Tti2 as a pleiotropic quantitative trait gene for adult hippocampal neurogenesis and serum glucose

0557065 - FGÚ 2023 RIV US eng J - Journal Article
Senko, A. N. - Overall, R. W. - Šilhavý, Jan - Mlejnek, Petr - Malínská, H. - Hüttl, M. - Marková, I. - Fabel, K. S. - Lu, L. - Stuchlík, Aleš - Williams, R. W. - Pravenec, Michal - Kempermann, G.
Systems genetics in the rat HXB/BXH family identifies Tti2 as a pleiotropic quantitative trait gene for adult hippocampal neurogenesis and serum glucose.
PLoS Genetics. Roč. 18, č. 4 (2022), č. článku e1009638. ISSN 1553-7404. E-ISSN 1553-7404
R&D Projects: GA ČR(CZ) GA20-00939S
Grant - others:AV ČR(CZ) AP1502
Program: Akademická prémie - Praemium Academiae
Institutional support: RVO:67985823
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)
Impact factor: 4.5, year: 2022
Method of publishing: Open access
https://doi.org/10.1371/journal.pgen.1009638

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.
Permanent Link: http://hdl.handle.net/11104/0331169