Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity.
Multiple organs cooperate to regulate appetite, metabolism, and glucose and fatty acid homeostasis. Here, we identified and characterized lymphatic vasculature dysfunction as a cause of adult-onset obesity. We found that functional inactivation of a single allele of the homeobox gene Prox1 led to adult-onset obesity due to abnormal lymph leakage from mispatterned and ruptured lymphatic vessels. Prox1 heterozygous mice are a new model for adult-onset obesity and lymphatic vascular disease.
Harvey
Natasha L
NL
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
Srinivasan
R Sathish
RS
Dillard
Miriam E
ME
Johnson
Nicole C
NC
Witte
Marlys H
MH
Boyd
Kelli
K
Sleeman
Mark W
MW
Oliver
Guillermo
G
D000483:Alleles; D000818:Animals; D004195:Disease Models, Animal; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000378:metabolism; D008196:Lymph / Q000378:metabolism; D044148:Lymphatic Abnormalities / Q000150:complications / Q000235:genetics*; D042601:Lymphatic Vessels / Q000002:abnormalities / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
D018398:Homeodomain Proteins; D007328:Insulin; D020738:Leptin; D008055:Lipids; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein