title: Mice Lacking Platelet-Derived Growth Factor D Display a Mild Vascular Phenotype.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Gladh
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erika Bergsten
authors.initials: EB
authors.lastname: Folestad
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Muhl
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Monika
authors.initials: M
authors.lastname: Ehnman
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.|Department of Surgical Sciences, Division of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Philip
authors.initials: P
authors.lastname: Tannenberg
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna-Lisa
authors.initials: AL
authors.lastname: Lawrence
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.|Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000648:ultrastructure; D001794:Blood Pressure; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005298:Fertility; D015870:Gene Expression; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism; D006321:Heart; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL / Q000235:genetics* / Q000502:physiology; D018345:Mice, Knockout; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D008222:Lymphokines; C498951:Pdgfd protein, mouse; D010982:Platelet-Derived Growth Factor; D005947:Glucose