Supplementary Material for: A Novel Ataxic Mutant Mouse Line Having Sensory Neuropathy Shows Heavy Iron Deposition in Kidney

<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