In vivo viability of postmitotic Purkinje neurons requires pRb family member function.
The product of the retinoblastoma susceptibility gene, pRb, is known to be an important regulator of cell division. Disrupted central nervous system development in RB null mice suggests a critical function for pRb in the proliferative arrest and initiation of terminal differentiation of certain neurons. Previously, we have shown that SV40 T-ag expression targeted to Purkinje neurons in transgenic mice causes cell-specific death. Here we describe that T-ag expression induces DNA synthesis and results in DNA fragmentation in Purkinje neurons. Characterization of transgenic mouse lines expressing mutant T-ags demonstrate that the pRb binding domain of T-ag is required for induction of Purkinje cell loss. These findings indicate that a pRb function is required well beyond the completion of Purkinje neuron differentiation and provide a link between cell cycle regulation and neurodegeneration in vivo.
Feddersen
R M
RM
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
Clark
H B
HB
Yunis
W S
WS
Orr
H T
HT
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000235:genetics; D002531:Cerebellum / Q000473:pathology; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D016161:Genes, Retinoblastoma / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*
D000952:Antigens, Polyomavirus Transforming; D004247:DNA