Functional analysis on the role of platelet-derived growth factor in CNS development after birth using knockout model.

1)Establishment of the model animal.We have found that the CNS is one of the organs that express platelet-derived growth factor(PDGF) and its receptors at high levels. However, their function still remains undetermined in CNS in vivo. To understand the function, we established conditional knockout mouse of PDGF beta-receptor(PDGFR-b) using Cre-loxP system in this project. Mice with foxed PDGFR-b allele do not show apparent abnormality. Now study is under process on the mice in which PDGFR-b is conditionally ablated only in CNS by the crossbreeding with Cre transgenic mice. These mice survive and grow up until adult, indicating that the model established in current study is useful for the functional study of PDGFR-b.2)Other studiesIn neonatal rat, we found that the PDGF-B chain expressed in CNS is important physiological modulator of the vulnerability of brain to excitotoxicity, which vulnerability is specific to neonatal period in both rodent and human. It was suggested that the enforcement of PDGF-B/PDGFR-b could protect the immature brain at risk of hypoxic and ischemic injury.We demonstrated that PDGF-B expression was induced in the process of sciatic nerve regeneration after crush injury. Furthermore, the active form of Src, a signaling molecule at the downstream of PDGFR, is also induced at the same time. Separately, we showed that the PDGF-B induced tubular epithelial cell regeneration via the activation of Src after ischemic insult of kidney. These findings obtained indicate that induction of PDGF-B signaling is important for the regeneration of nerve and kidney.We conducted studies on basic aspects of brain development focusing on the expression of ZFH transcription factors. Also we studied on FGF, Klotho gene.In summary, we established mouse model to study the function of PDGF based on Cre/loxP system. We are starting to obtain data indicating the significance of PDGF in CNS. Further study would be required.