JAX Mice for Ataxia research - The Jackson Laboratory

Ataxia

Ataxia is a collective term used to describe a variety of progressive, neurodegenerative, variable onset, often hereditary diseases that typically result in poor coordination, slurred speech, and other symptoms (National Ataxia Foundation, www.ataxia.org).

JAX^® Mice Models

B6CBACa A^w-J/A-Aifm1^Hq/J (Stock Number 000501)

Harlequin mice are so called because hemizygous males and homozygous females are nearly bald (baldness in heterozygous females is patchy and not always obvious). Harlequin mice develop a noticeable and progressive ataxia (initially manifesting itself as a side-to-side unsteady gait and a lateral tremor at rest) by the time they are five months old. When they are four months old, they exhibit a delayed cerebellar cortical atrophy characterized by granule cell death and subsequent Purkinje cell death. Whereas the granule cells re-enter the cell cycle, the Purkinje cells do not, supporting the postulate that inappropriate cell cycle re-entry of terminally differentiated neurons induces apoptosis. They exhibit progressive retinal degeneration from the time they are three months old. Heterozygous females do not develop cerebellar and retinal abnormalities. Homozygotes and hemizygous males weigh less than either heterozygous or wild–type controls. Hemizygous males, homozygous females, and hemizygous females are all viable and fertile.

Reference

Klein JA, Longo-Guess CM, Rossmann MP, Seburn KL, Hurd RE, Frankel WN, Bronson RT, Ackerman SL. 2002. The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature 419:367-74.

C3H/HeSnJ-Ctnna2^cdf/J (Stock Number 002235)

Cerebellar deficient folia (cdf), a recessive mutation on Chromosome 6, causes a hypoplastic and dysmorphic cerebellum. On the C3H/HeJ background, cdf homozygotes have only seven cerebellar folia rather than the ten present in wild–type mice, and the folia pattern is abnormal. Their vermis is two-thirds the length of those in wild–type controls, and their ventral vermis contains concentric mineral deposits. Their cerebellum contains ectopic Purkinje cells, appearing to be the failure of the zebrin II-negative subpopulation to disperse. The overall number of Purkinje cells in homozygotes is relatively normal.

By the time they are two weeks old, homozygotes for the mutation have a constant side-to-side wobble, often holding their tails in the air and arching them over their heads. Homozygotes weigh about 25% and 50% less than littermate controls at weaning and as adults respectively. Whereas they live a normal life span (one-and-a-half to two years on the C3H/HeJ background), homozygous males rarely breed, and homozygous females are poor mothers, requiring transfer of litters to foster mothers.

References

Park C, Falls W, Finger JH, Longo-Guess CM, Ackerman SL. 2002. Deletion in Catna2, encoding alpha N-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation. Nat Genet 31:279-84.

Marzban H, Khanzada U, Shabir S, Hawkes R, Langnaese K, Smalla KH, Bockers TM, Gundelfinger ED, Gordon-Weeks PR, Beesley PW. 2003. Expression of the immunoglobulin superfamily neuroplastin adhesion molecules in adult and developing mouse cerebellum and their localization to parasagittal stripes. J Comp Neurol 462:286-301.