<p><b><i>Background/Aims:</i></b> A novel ataxic mouse line was
established from the offspring of a male mouse administered
cyclophosphamide in a juvenile period. <b><i>Methods:</i></b> We have
attempted to examine the phenotype and histopathological changes of
affected mice. Furthermore, linkage analysis and sequencing of the
mutant was performed to reveal the causative gene locus. <b><i>Results and Conclusion:</i></b>
The affected mouse was characterized by heavy hind limb ataxia with
gait disorder, which was first recognized at about 4 weeks of age and
slowly progressed with advancing age. The phenotype was inherited in an
autosomal recessive pattern. The genetic locus associated with the
phenotype was named <i>hak</i> and mapped to 107,305,356-108,637,615 on chromosome 2qE3, non-coding sequences in the vicinity of <i>Bdnf</i>
gene. Many spheroids were noticed in the cerebellar medulla and the
brain stem. In the peripheral nerves, some sensory ganglionic cells
showed deposition of NF-200 in the perikaryon and NF-200-positive
spheroids in nerve fibers. No inflammatory cell infiltration was
observed. In addition, the adult affected mouse had distinct iron
deposition in the kidney and the liver, but not in the heart, the
skeletal muscle and the central nervous system. These results suggest
that the <i>hak</i> mouse has a tissue-specific impairment in the expression of a type of <i>Bdnf</i> transcripts.</p