Mice Lacking Platelet-Derived Growth Factor D Display a Mild Vascular Phenotype

• Published in: PloS one Vol. 11; no. 3; p. e0152276
• Main Authors: Gladh, Hanna, Folestad, Erika Bergsten, Muhl, Lars, Ehnman, Monika, Tannenberg, Philip, Lawrence, Anna-Lisa, Betsholtz, Christer, Eriksson, Ulf
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31-03-2016; Public Library of Science (PLoS)
• Subjects: Animal tissues; Animals; Arteries - metabolism; Arteries - ultrastructure; Atherosclerosis; Bifurcations; Biochemistry; Biology; Biology and Life Sciences; Biophysics; Blood; Blood platelets; Blood Pressure; Cardiovascular disease; Deactivation; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Female; Fertility; Gene Expression; Gene Knockout Techniques; Genetic aspects; Genomes; Glucose - metabolism; Growth factors; Heart; Heart diseases; Homeostasis; Hypertension; Inactivation; Kinases; Ligands; Lymphokines - genetics; Male; Medical research; Medicin och hälsovetenskap; Medicine and Health Sciences; Mice; Mice, Inbred C57BL - genetics; Mice, Inbred C57BL - physiology; Mice, Knockout; Offspring; Pathology; Pericytes; Phenotype; Physiological aspects; Physiology; Platelet-derived growth factor; Platelet-Derived Growth Factor - genetics; Promoter Regions, Genetic; Reporter gene; Research and Analysis Methods; Rodents; Smooth muscle; Studies; Subpopulations; Tissue analysis; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152276

Platelet-derived growth factor D (PDGF-D) is the most recently discovered member of the PDGF family. PDGF-D signals through PDGF receptor β, but its biological role remains largely unknown. In contrast to other members of the PDGF family of growth factors, which have been extensively investigated using different knockout approaches in mice, PDGF-D has until now not been characterized by gene inactivation in mice. Here, we present the phenotype of a constitutive Pdgfd knockout mouse model (Pdgfd-/-), carrying a LacZ reporter used to visualize Pdgfd promoter activity. Inactivation of the Pdgfd gene resulted in a mild phenotype in C57BL/6 mice, and the offspring was viable, fertile and generally in good health. We show that Pdgfd reporter gene activity was consistently localized to vascular structures in both postnatal and adult tissues. The expression was predominantly arterial, often localizing to vascular bifurcations. Endothelial cells appeared to be the dominating source for Pdgfd, but reporter gene activity was occasionally also found in subpopulations of mural cells. Tissue-specific analyses of vascular structures revealed that NG2-expressing pericytes of the cardiac vasculature were disorganized in Pdgfd-/- mice. Furthermore, Pdgfd-/- mice also had a slightly elevated blood pressure. In summary, the vascular expression pattern together with morphological changes in NG2-expressing cells, and the increase in blood pressure, support a function for PDGF-D in regulating systemic arterial blood pressure, and suggests a role in maintaining vascular homeostasis.