title: In vivo viability of postmitotic Purkinje neurons requires pRb family member function.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Feddersen
authors.forename: H B
authors.initials: HB
authors.lastname: Clark
authors.forename: W S
authors.initials: WS
authors.lastname: Yunis
authors.forename: H T
authors.initials: HT
authors.lastname: Orr
mesh_terms: 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*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004247:DNA