Atm expression patterns suggest a contribution from the peripheral nervous system to the phenotype of ataxia-telangiectasia

Ataxia-telangiectasiais a human autosomal recessive disease characterized by neurodegeneration, cancer predisposition and sensitivity to ionizing radiation. One of the earliest features of this disease is ataxia, which is thought to be attributable to a progressive cerebellar degeneration associated with a disruption of Purkinje cell cytoarchitecture and positioning. To investigate the neuropathology of ataxia-telangiectasia, we used in situ hybridization to map Atm (the gene mutated in ataxia-telangiectasia) expression during mouse development. Atm expression was highest in the embryonic mouse nervous system, where it was predominantly associated with regions undergoing mitosis. During the period of Purkinje cell neurogenesis, Arm was highly expressed in the area containing Purkinje cell precursors (the ventricular zone of the fourth ventricle). However, in the postnatal cerebellum, Atm expression in Purkinje cells was very low, while expression in proliferating granule neurons was high. The only region of the adult nervous system that exhibited elevated Arm expression were the postmitotic sensory neurons of the dorsal root ganglia. The data suggest an early developmental requirement for ATM in the cerebellum and other regions of the central nervous system, and a potential contribution of the dorsal root ganglia/sensory input pathway to the ataxic phenotype of ataxia-telangiectasia. (C) 1998 IBRO. Published by Elsevier Science Ltd.