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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F22%3A00557065" target="_blank" >RIV/67985823:_____/22:00557065 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1371/journal.pgen.1009638" target="_blank" >https://doi.org/10.1371/journal.pgen.1009638</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pgen.1009638" target="_blank" >10.1371/journal.pgen.1009638</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

<a href="/cs/project/GA20-00939S" target="_blank" >GA20-00939S: Neuronální populace a okruhy kódující paměťové stopy pro časové asociace jako základní biologický model epizodické formy deklarativní paměti</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PLoS Genetics

ISSN

1553-7404

e-ISSN

1553-7404

Svazek periodika

18

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

35

Strana od-do

e1009638

Kód UT WoS článku

000780213300003

EID výsledku v databázi Scopus

2-s2.0-85128526029