title: Dll1 haploinsufficiency in adult mice leads to a complex phenotype affecting metabolic and immunological processes.
abstract: BACKGROUND
  The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage.
  
  
  RESULTS
  Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized.
  
  
  CONCLUSIONS
  In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes.
authors: Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Isabel
authors: I
authors: Rubio-Aliaga
authors: Gerhard K H
authors: GK
authors: Przemeck
authors: Helmut
authors: H
authors: Fuchs
authors: Valérie
authors: V
authors: Gailus-Durner
authors: Thure
authors: T
authors: Adler
authors: Wolfgang
authors: W
authors: Hans
authors: Marion
authors: M
authors: Horsch
authors: Birgit
authors: B
authors: Rathkolb
authors: Jan
authors: J
authors: Rozman
authors: Anja
authors: A
authors: Schrewe
authors: Sibylle
authors: S
authors: Wagner
authors: Sabine M
authors: SM
authors: Hoelter
authors: Lore
authors: L
authors: Becker
authors: Thomas
authors: T
authors: Klopstock
authors: Wolfgang
authors: W
authors: Wurst
authors: Eckhard
authors: E
authors: Wolf
authors: Martin
authors: M
authors: Klingenspor
authors: Boris T
authors: BT
authors: Ivandic
authors: Dirk H
authors: DH
authors: Busch
authors: Johannes
authors: J
authors: Beckers
authors: Martin
authors: M
authors: Hrabé de Angelis
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008024:Ligands; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D051880:Receptors, Notch