Neuron-specific ablation of PDGF-B is compatible with normal central nervous system development and astroglial response to injury.
Members of the PDGF family have multiple roles during embryogenesis and in a variety of pathological situations in the adult. One of the major sites of PDGF-B expression in adult mammals are postmitotic CNS neurons. Combined with reported neurotrophic and neuroprotective effects of exogenously administered PDGFs, this has led to the speculation that PDGF-B may have a role in CNS development, in maintenance, or in response to CNS injury. To test these hypotheses, we developed mice in which PDGF-B was ablated genetically in postmitotic neurons at sites where PDGF-B is normally expressed. We found that these mice develop to adulthood without apparent defects. We demonstrate PDGF-B expression in the postnatal mouse hippocampus and forebrain cortex. We show that neuron-specific knockout of PDGF-B does not influence the astroglial and angiogenic responses to injury in the hippocampus or forebrain cortex. We conclude that the role of neuron-derived PDGF-B remains obscure. A role for neuron-derived PDGF-B, if existing, might be redundant with other CNS growth factors. Alternatively, other and more specific analyses of CNS functions in the normal and injured states will be required to demonstrate such a role.
Enge
Maria
M
Department of Medical Biochemistry, Göteborg University, Göteborg, Sweden.
Wilhelmsson
Ulrika
U
Abramsson
Alexandra
A
Stakeberg
Josefina
J
Kühn
Ralf
R
Betsholtz
Christer
C
Pekny
Milos
M
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001483:Base Sequence; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017931:DNA Primers; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger