Hypermetabolism in mice carrying a near complete human chromosome 21.


Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
31 Jan 2023
Historique:
entrez: 13 2 2023
pubmed: 14 2 2023
medline: 14 2 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 due to sarcolipin overexpression in the skeletal muscle, resulting in futile sarco(endo)plasmic reticulum Ca

Identifiants

pubmed: 36778465
doi: 10.1101/2023.01.30.526183
pmc: PMC9915508
pii:
doi:

Types de publication

Preprint

Langues

eng

Commentaires et corrections

Type : UpdateIn

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Auteurs

Dylan C Sarver (DC)

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Cheng Xu (C)

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Susana Rodriguez (S)

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Susan Aja (S)

Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Andrew E Jaffe (AE)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
The Lieber Institute for Brain Development, Baltimore, MD, USA.
Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA.
Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Feng J Gao (FJ)

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Michael Delannoy (M)

Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Muthu Periasamy (M)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA.
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.

Yasuhiro Kazuki (Y)

Division of Genome and Cellular Functions, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Tottori, Japan.
Chromosome Engineering Research Center, Tottori University, Tottori, Japan.

Mitsuo Oshimura (M)

Chromosome Engineering Research Center, Tottori University, Tottori, Japan.

Roger H Reeves (RH)

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

G William Wong (GW)

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Classifications MeSH