Increased body fat in mice with a targeted mutation of the paternally expressed imprinted gene Peg3.
Peg3 encodes a C2H2 type zinc finger protein that is implicated in a novel physiological pathway regulating core body temperature, feeding behavior, and obesity in mice. Peg3+/- mutant mice develop an excess of abdominal, subcutaneous, and intra-scapular fat, despite a lifetime of lower food intake than wild-type animals. However, they start life with reduced fat reserves and are slower to enter puberty. These mice maintain a lower core body temperature, fail to respond to a cold challenge, and have lower metabolic activity as measured by oxygen consumption. Plasma leptin levels are significantly higher than in wild types, and Peg3+/- mice appear to have developed leptin resistance. Administration of exogenous leptin resulted in a significant reduction in food intake in wild-type mice that was not observed in Peg3+/- mutants. This mutation, which is strongly expressed in hypothalamic tissue during development, has the capacity to regulate multiple events relating to energy homeostasis.
Curley
J P
JP
Sub-Department of Animal Behavior, University of Cambridge, Madingley, Cambridge, UK. jpc38@cam.ac.uk
Pinnock
S B
SB
Dickson
S L
SL
Thresher
R
R
Miyoshi
N
N
Surani
M A
MA
Keverne
E B
EB
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D001831:Body Temperature; D001835:Body Weight; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism; D005260:Female; D007031:Hypothalamus / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D020738:Leptin / Q000097:blood / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity; D009154:Mutation; D009478:Neuropeptide Y / Q000235:genetics; D009765:Obesity / Q000209:etiology; D010101:Oxygen Consumption; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012741:Sexual Maturation; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D051741:Kruppel-Like Transcription Factors; D020738:Leptin; D009478:Neuropeptide Y; C097901:Peg3 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin; D011494:Protein Kinases