Analysis of Mice Lacking the Heparin-Binding Splice Isoform of Platelet-Derived Growth Factor A
Författare
Summary, in English
Platelet-derived growth factor A-chain (PDGF-A) exists in two evolutionarily conserved isoforms, PDGF-Along and PDGF-Ashort, generated by alternative RNA splicing. They differ by the presence (in PDGF-Along) or absence (in PDGF-Ashort) of a carboxyterminal heparin/heparan sulfate proteoglycan-binding motif. In mice, similar motifs present in other members of the PDGF and vascular endothelial growth factor (VEGF) families have been functionally analyzed in vivo, but the specific physiological importance of PDGF-A(long) has not been explored previously. Here, we analyzed the absolute and relative expression of the two PDGF-A splice isoforms during early postnatal organ development in the mouse and report on the generation of a Pdgfa allele (Pdgfa(Delta ex6) incapable of producing PDGF-A(long) due to a deletion of the exon 6 splice acceptor site. In situations of limiting PDGF-A signaling through PDGF receptor alpha (PDGFR alpha), or in mice lacking PDGF-C, homozygous carriers of Pdgfa(Delta ex6) showed abnormal development of the lung, intestine, and vertebral column, pinpointing developmental processes where PDGF-A(long) may play a physiological role.
Avdelning/ar
- Avdelningen för klinisk genetik
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2013
Språk
Engelska
Sidor
4030-4040
Publikation/Tidskrift/Serie
Molecular and Cellular Biology
Volym
33
Issue
20
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Microbiology
Ämne
- Medical Genetics
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0270-7306