Imprinted gene dosage is critical for the transition to independent life.
Neonatal survival in mammals is crucially dependent upon maintenance of body temperature. Neonatal body temperature is largely maintained by thermogenesis in brown adipose tissue (BAT). BAT develops perinatally in mice requiring integration of adipogenic and thermoregulatory gene pathways. We describe a regulatory mutation in the imprinted gene cluster on mouse chromosome 12 resulting in early postnatal lethality. Maternal inheritance of this mutation impairs the ability of young mice to maintain body temperature. While mechanisms of perinatal BAT development are well understood, our work highlights a second phase of BAT recruitment necessary to support small animals newly independent of the nest. We show that the imprinted delta-like homolog 1/preadipocyte factor (Dlk1/Pref1) and iodothyronine deiodinase type 3 (Dio3) functions converge on the development of brown fat at the transition to independent life. This shows that appropriate dosage control at imprinted loci can act as a critical determinant in postnatal survival during phases of physiological adaptation.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. mc524@cam.ac.uk
Marika
M
Charalambous
Sacramento R
SR
Ferron
Simao T
ST
da Rocha
Andrew J
AJ
Murray
Timothy
T
Rowland
Mitsuteru
M
Ito
Karin
K
Schuster-Gossler
Arturo
A
Hernandez
Anne C
AC
Ferguson-Smith
D000222:Adaptation, Physiological / Q000235:genetics* / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D002135:Calcium-Binding Proteins; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D018628:Gene Dosage / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology; D007453:Iodide Peroxidase / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010101:Oxygen Consumption / Q000502:physiology; D018709:Statistics, Nonparametric; D022722:Thermogenesis / Q000235:genetics* / Q000502:physiology
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase