Hypermetabolism in mice carrying a near-complete human chromosome 21.
SERCA pump
aneuploidy
chromosomes
futile cycle
gene expression
hypermetabolism
mouse
sarcolipin
trisomy
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
30 05 2023
30 05 2023
Historique:
received:
07
01
2023
accepted:
07
05
2023
medline:
1
6
2023
pubmed:
30
5
2023
entrez:
30
5
2023
Statut:
epublish
Résumé
The consequences of aneuploidy have traditionally been studied in cell and animal models in which the extrachromosomal DNA is from the same species. Here, we explore a fundamental question concerning the impact of aneuploidy on systemic metabolism using a non-mosaic transchromosomic mouse model (TcMAC21) carrying a near-complete human chromosome 21. Independent of diets and housing temperatures, TcMAC21 mice consume more calories, are hyperactive and hypermetabolic, remain consistently lean and profoundly insulin sensitive, and have a higher body temperature. The hypermetabolism and elevated thermogenesis are likely due to a combination of increased activity level and sarcolipin overexpression in the skeletal muscle, resulting in futile sarco(endo)plasmic reticulum Ca
Identifiants
pubmed: 37249575
doi: 10.7554/eLife.86023
pii: 86023
pmc: PMC10229126
doi:
pii:
Substances chimiques
Proteolipids
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK084171
Pays : United States
Organisme : NIDDK NIH HHS
ID : U2C DK135066
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023, Sarver et al.
Déclaration de conflit d'intérêts
DS, CX, SR, SA, AJ, FG, MD, MP, YK, RR, GW No competing interests declared, MO M.O. is CEO, employee, and shareholder of Trans Chromosomics, Inc which manages commercial use of the TcMAC21 mouse. We declare that none of the authors has a conflict of interest
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