Analysis of Mice Lacking the Heparin-Binding Splice Isoform of Platelet-Derived Growth Factor A

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • Johanna Andrae
  • Hans Ehrencrona
  • Radiosa Gallini
  • Mark Lal
  • Hao Ding
  • Christer Betsholtz
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
Originalspråkengelska
Sidor (från-till)4030-4040
TidskriftMolecular and Cellular Biology
Volym33
Utgivningsnummer20
StatusPublished - 2013
PublikationskategoriForskning
Peer review utfördJa