Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells.
All blood capillaries consist of endothelial tubes surrounded by mural cells referred to as pericytes. The origin, recruitment, and function of the pericytes is poorly understood, but the importance of these cells is underscored by the severe cardiovascular defects in mice genetically devoid of factors regulating pericyte recruitment to embryonic vessels, and by the association between pericyte loss and microangiopathy in diabetes mellitus. A general problem in the study of pericytes is the shortage of markers for these cells. To identify new markers for pericytes, we have taken advantage of the platelet-derived growth factor (PDGF)-B knockout mouse model, in which developing blood vessels in the central nervous system are almost completely devoid of pericytes. Using cDNA microarrays, we analyzed the gene expression in PDGF-B null embryos in comparison with corresponding wild-type embryos and searched for down-regulated genes. The most down-regulated gene present on our microarray was RGS5, a member of the RGS family of GTPase-activating proteins for G proteins. In situ hybridization identified RGS5 expression in brain pericytes, and in pericytes and vascular smooth muscle cells in certain other, but not all, locations. Absence of RGS5 expression in PDGF-B and PDGFR beta-null embryos correlated with pericyte loss in these mice. Residual RGS5 expression in rare pericytes suggested that RGS5 is a pericyte marker expressed independently of PDGF-B/R beta signaling. With RGS5 as a proof-of-principle, our data demonstrate the usefulness of microarray analysis of mouse models for abnormal pericyte development in the identification of new pericyte-specific markers.
Bondjers
Cecilia
C
Department of Medical Biochemistry, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Kalén
Mattias
M
Hellström
Mats
M
Scheidl
Stefan J
SJ
Abramsson
Alexandra
A
Renner
Oliver
O
Lindahl
Per
P
Cho
Hyeseon
H
Kehrl
John
J
Betsholtz
Christer
C
D000818:Animals; D000077214:Becaplermin; D015415:Biomarkers; D016172:DNA Fingerprinting; D004622:Embryo, Mammalian; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology*; D020411:Oligonucleotide Array Sequence Analysis; D020286:Pericytes / Q000166:cytology*; D010982:Platelet-Derived Growth Factor / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D011247:Pregnancy; D020574:Proto-Oncogene Proteins c-sis; D020710:RGS Proteins / Q000032:analysis* / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
D015415:Biomarkers; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D020710:RGS Proteins; C105346:Rgs5 protein, mouse; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D019204:GTP-Binding Proteins