Get access

Locomotor and oculomotor impairment associated with cerebellar dysgenesis in Zic3-deficient (Bent tail) mutant mice

Authors

  • Jun Aruga,

    1. Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama 351–0198, Japan
    Search for more papers by this author
  • Hiroo Ogura,

    1. Tsukuba Research Laboratories, Eisai Co. Ltd, Tsukuba-shi, Ibaraki 300–2635, Japan
    Search for more papers by this author
  • Fumihiro Shutoh,

    1. Laboratory for Motor Learning Control, RIKEN Brain Science Institute, Wako-shi, Saitama 351–0198, Japan
    2. CREST, JST, Kawaguchi-shi, Saitama 332–0012, Japan
    Search for more papers by this author
  • Miyuki Ogawa,

    1. Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama 351–0198, Japan
    2. Division of Molecular Neurobiology, Department of Basic Medical Science, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108–8639, Japan
    Search for more papers by this author
  • Barbara Franke,

    1. Department of Human Genetics, University Medical Centre Nijmegen, 6500HB Nijmegen, the Netherlands
    Search for more papers by this author
  • Soichi Nagao,

    1. Laboratory for Motor Learning Control, RIKEN Brain Science Institute, Wako-shi, Saitama 351–0198, Japan
    2. CREST, JST, Kawaguchi-shi, Saitama 332–0012, Japan
    Search for more papers by this author
  • Katsuhiko Mikoshiba

    1. Division of Molecular Neurobiology, Department of Basic Medical Science, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108–8639, Japan
    2. Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako-shi, Saitama 351–0198, Japan
    Search for more papers by this author

Jun Aruga, 1Laboratory for Comparative Neurogenesis, as above.
E-mail: jaruga@brain.riken.go.jp

Abstract

We examined the adult neural phenotypes of the Bent tail mutant mouse. The Bent tail mutant mouse was recently shown to lack a submicroscopic part of the X chromosome containing the Zic3 gene, which encodes a zinc-finger protein controlling vertebrate neural development. While nearly one-fourth of hemizygous Bent tail (Bn/Y, Zic3-deficient) mice developed neural tube defects in their midbrain and hindbrain region, the other Bn/Y mice showed apparently normal behaviour in a C57BL/6 genetic background. A battery of behavioural and eye movement tests revealed impaired spontaneous locomotor activity, reduction of muscle tone and impairments of vestibuloocular and optokinetic eye movements in these mice. Morphological examination of the mutant brain showed a significant reduction in the cell numbers in the cerebellar anterior lobe and paraflocculus–flocculus complex. Our results indicate that the cerebellar dysgenesis characterized by subregional hypoplasia affects the locomotor activity, muscle tone and eye movement control of the mice. These findings may have some clinical implications in relation to disorders characterized by cerebellar dysgenesis, such as Joubert syndrome.

Ancillary