PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Lee, A.W.* ; Hengstler, H.* ; Schwald, K.* ; Berriel Diaz, M.* ; Loreth, D.* ; Kirsch, M.* ; Kretz, O.* ; Haas, C.A.* ; Hrabě de Angelis, M. ; Herzig, S.* ; Brümmendorf, T.* ; Klingenspor, M.* ; Rathjen, F.G.* ; Rozman, J. ; Nicholson, G.* ; Cox, R.D.* ; Schäfer, M.K.*

Functional inactivation of the genome-wide association study obesity gene neuronal growth regulator 1 in mice causes a body mass phenotype.

PLoS ONE 7:e41537 (2012)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
To date, genome-wide association studies (GWAS) have identified at least 32 novel loci for obesity and body mass-related traits. However, the causal genetic variant and molecular mechanisms of specific susceptibility genes in relation to obesity are yet to be fully confirmed and characterised. Here, we examined whether the candidate gene NEGR1 encoding the neuronal growth regulator 1, also termed neurotractin or Kilon, accounts for the obesity association. To characterise the function of NEGR1 for body weight control in vivo, we generated two novel mutant mouse lines, including a constitutive NEGR1-deficient mouse line as well as an ENU-mutagenised line carrying a loss-of-function mutation (Negr1-I87N) and performed metabolic phenotypic analyses. Ablation of NEGR1 results in a small but steady reduction of body mass in both mutant lines, accompanied with a small reduction in body length in the Negr1-I87N mutants. Magnetic resonance scanning reveals that the reduction of body mass in Negr1-I87N mice is due to a reduced proportion of lean mass. Negr1-I87N mutants display reduced food intake and physical activity while normalised energy expenditure remains unchanged. Expression analyses confirmed the brain-specific distribution of NEGR1 including strong expression in the hypothalamus. In vitro assays show that NEGR1 promotes cell-cell adhesion and neurite growth of hypothalamic neurons. Our results indicate a role of NEGR1 in the control of body weight and food intake. This study provides evidence that supports the link of the GWAS candidate gene NEGR1 with body weight control.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.092
0.000
40
50
Tags
GMC
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Obesity; NEGR1; GWAS; body weight control; CELL-ADHESION MOLECULE; INCREASED ENERGY-EXPENDITURE; EPITHELIAL OVARIAN-CANCER; NEURITE OUTGROWTH; IGLON FAMILY; HETEROPHILIC INTERACTIONS; TUMOR-SUPPRESSOR; NERVOUS-SYSTEM; DEFICIENT MICE; RAT-BRAIN
Sprache englisch
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 7, Heft: 7, Seiten: , Artikelnummer: e41537 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Institute of Diabetes and Cancer (IDC)
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500600-003
G-500600-001
G-501900-066
G-501900-063
PubMed ID 22844493
DOI 10.1371/journal.pone.0041537
WOS ID WOS:000306687700105
Scopus ID 84864488946
Erfassungsdatum 2012-08-21
[➜Korrektur melden]