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Published on: October 7, 2021
Generation of conditional knockout alleles for PDGF-C
1Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
Insights
Platelet-derived growth factor-C (PDGF-C) is crucial for embryonic development, as its absence causes perinatal lethality. New conditional alleles of the Pdgf-c gene enable detailed study of PDGF-C
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Platelet-derived growth factor-C (PDGF-C) is a key signaling molecule in the PDGF family.
- PDGF-C interacts with PDGF receptor (PDGFR)-alphaalpha and alphabeta dimers to regulate cellular functions.
- PDGF-C deficiency leads to perinatal lethality, characterized by cleft palate formation.
Purpose of the Study:
- To further characterize the cellular functions of PDGF-C during embryonic and postnatal development.
- To generate conditional alleles of the Pdgf-c gene for precise spatial and temporal gene manipulation.
- To establish an efficient method for creating conditional mouse alleles.
Main Methods:
- Generation of two conditional alleles for the Pdgf-c gene, flanking exon 5 with loxP sites.
- Utilizing global Cre-mediated excision to delete the floxed exon 5.
- Phenotypic analysis of resulting PDGF-C deficient embryos.
Main Results:
- Global Cre-mediated deletion resulted in a complete loss of PDGF-C expression.
- Embryonic defects observed were identical to those of PDGF-C null embryos, including cleft palate.
- The generated conditional alleles serve as valuable tools for studying PDGF-C roles.
Conclusions:
- Conditional alleles of Pdgf-c are essential genetic tools for dissecting PDGF-C's roles in development and adult tissues.
- These alleles facilitate the study of PDGF-C's spatial and temporal functions.
- An efficient approach for creating mouse conditional alleles was successfully demonstrated.
Abstract:
PDGF-C is a newly identified member of the platelet-derived growth factor (PDGF) family, which is involved in multiple cellular functions by signaling through PDGF receptor (PDGFR)-alphaalpha and alphabeta dimers. PDGF-C deficiency is perinatal lethal due to the formation of cleft palate. To further characterize the cellular function of PDGF-C during both embryonic and postnatal development, we have generated two conditional alleles of the Pdgf-c gene in which two loxP sites flank exon 5. Global Cre-mediated excision of the floxed exon 5 in these alleles resulted in a complete loss of PDGF-C expression and caused embryonic defects identical to those previously described for the PDGF-C null embryos. These conditional alleles will therefore be the important genetic tools for dissecting the spatial and temporal roles of PDGF-C during development and in adult tissues. Furthermore, from this work, we have also described a simple approach for creating mouse conditional alleles in an efficient manner.
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