Scrambler mouse

Scrambler is a spontaneous mouse mutant lacking a functional DAB1 gene, resulting in a phenotype resembling that seen in the reeler mouse. The strain was first described by Sweet et al in 1996.

Neuroanatomical abnormalities
The spontaneous autosomal recessive scrambler mutation on chromosome 4 causes a deficiency of DAB1, encoding disabled-1, a protein involved in the signaling of the Reelin protein, lacking in the reeler mutant, Dba1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in cerebellar cortex, hippocampus, and neocortex. Purkinje cell and granule cell degeneration results in ataxia. Despite normal Reln mRNA levels, Dba1-scm mutants have defective reelin signaling, indicating that disabled-1 acts downstream of reelin. Cell ectopias are identical with targeted disruption of Dba1.

Behavioral abnormalities
Dab1-scm mutants have a wide-spread gait obvious to the naked eye (ataxia). In their home-cage, they often reel and fall, especially when attempting to rear up against the walls. Nevertheless, the mutants are fertile, and so can be reproduced from one generation to the next. Relative to non-ataxic controls of the same background strain, Dab1-scm mutants are impaired in the Rotarod Performance test of motor coordination as well as a grid-climbing test. When picked up by the tail, they show a pathological reflex, limb-clasping, characterized by holding together fore- or hind-limbs, or all four together in a bat-like posture.