Conditional deletions refine the embryonic requirement for Dlk1

• Published in: Mechanisms of development Vol. 130; no. 2-3; pp. 143 - 159
• Main Authors: Appelbe, Oliver K., Yevtodiyenko, Aleksey, Muniz-Talavera, Hilmarie, Schmidt, Jennifer V.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.02.2013
• Subjects: Animals; Conditional knockout; Diet, High-Fat; Dlk1; Embryonic Development - genetics; Endothelial cell; Endothelial Cells - metabolism; Female; Gene Deletion; Genes, Lethal; Insulin-Secreting Cells - metabolism; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Intra-Abdominal Fat - growth & development; Intra-Abdominal Fat - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Organ Size; Organ Specificity; Pancreas; Pancreas - cytology; Pancreas - growth & development; Pituitary; Pituitary Gland - cytology; Pituitary Gland - growth & development; Placenta - anatomy & histology; Placenta - metabolism; Pregnancy; Somatotrophs - metabolism; Conditional knockout; Endothelial cell; Pancreas; Pituitary; Dlk1
• ISSN: 0925-4773; 1872-6356; 1872-6356
• DOI: 10.1016/j.mod.2012.09.010

► Dlk1flox mice were generated to allow conditional deletion of the Dlk1 gene. ► Dlk1cons null mutants display perinatal death and reduced growth of survivors. ► Increased cellularity of Dlk1cons placentae may limit maternal-fetal exchange. ► Loss of Dlk1 in beta cells, somatotropes or endothelial cells causes no pathology. Numerous studies have implicated Delta-like 1 (DLK1), a transmembrane protein that shares homology with Notch ligands, in embryonic growth and differentiation. Dlk1 expression is widespread, though not ubiquitous, during early development, but is confined to a few specific cell types in adults. Adult Dlk1-expressing tissues include the Insulin-producing β-cells of the pancreas and the Growth hormone-producing somatotrophs of the pituitary gland. Previously generated Dlk1 null mice (Dlk1Sul-pat), display a partially penetrant neonatal lethality and a complex pattern of developmental and adult phenotypes. Here we describe the generation of a conditional Dlk1 mouse line (Dlk1flox) to facilitate cell type-specific deletion of the Dlk1 gene, providing a powerful system to explore each aspect of the Dlk1 null phenotype. Four tissue-specific Cre mouse lines were used to produce individual Dlk1 deletions in pancreatic β-cells, pituitary somatotrophs and the endothelial cells of the embryo and placenta, key candidates for the Dlk1 phenotype. Contrary to expectations, all of these conditional mice were fully viable, and none recapitulated any aspect of the Dlk1Sul-pat null mice. Dlk1 expression is therefore not essential for the normal development of β-cells, somatotrophs and endothelial cells, and the tissues responsible for the Dlk1 null phenotype remain to be identified. Dlk1flox mice will continue to provide an important tool for further research into the function of Dlk1.