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Updated: May 8, 2026
Purification of Platelets from Mouse Blood
Published on: May 7, 2019
Analysis of mice lacking the heparin-binding splice isoform of platelet-derived growth factor A
Johanna Andrae1, Hans Ehrencrona, Radiosa Gallini
1Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden.
Insights
Platelet-derived growth factor A-long (PDGF-A-long) is crucial for normal mouse organ development. Its absence leads to abnormalities in the lung, intestine, and vertebral column.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Platelet-derived growth factor A-chain (PDGF-A) has two isoforms: PDGF-A-long and PDGF-A-short, differing by a proteoglycan-binding motif.
- The in vivo function of PDGF-A-long has not been previously explored, despite its evolutionary conservation.
Purpose of the Study:
- To investigate the physiological importance of PDGF-A-long during early postnatal organ development in mice.
- To analyze the expression patterns of PDGF-A splice isoforms.
- To generate and study a mouse model lacking PDGF-A-long.
Main Methods:
- Analysis of PDGF-A isoform expression during early postnatal development.
- Generation of a Pdgfa allele (Pdgfa(Δex6)) to specifically delete PDGF-A-long.
- Phenotypic analysis of Pdgfa(Δex6) homozygous mice, particularly in contexts of limited PDGF-A signaling or PDGF-C deficiency.
Main Results:
- Homozygous Pdgfa(Δex6) mice exhibited abnormal development of the lung, intestine, and vertebral column.
- These developmental defects were observed under conditions of limited PDGF receptor alpha (PDGFRα) signaling or in PDGF-C-deficient mice.
- The study provides evidence for the specific roles of PDGF-A-long in these developmental processes.
Conclusions:
- PDGF-A-long plays a critical physiological role in the development of the lung, intestine, and vertebral column.
- The findings highlight the importance of alternative splicing in generating functional diversity for growth factors.
- Further research can elucidate the precise mechanisms by which PDGF-A-long influences organogenesis.
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 carboxy-terminal 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-Along 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(Δex6)) incapable of producing PDGF-Along due to a deletion of the exon 6 splice acceptor site. In situations of limiting PDGF-A signaling through PDGF receptor alpha (PDGFRα), or in mice lacking PDGF-C, homozygous carriers of Pdgfa(Δex6) showed abnormal development of the lung, intestine, and vertebral column, pinpointing developmental processes where PDGF-Along may play a physiological role.
