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The Disabled-1 (Dab1) gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells . DAB1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain and during adult neurogenesis .
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, [3] Dab1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in cerebellar cortex, hippocampus, and neocortex.
It was then demonstrated that the mouse disabled homologue 1 gene is responsible for the phenotypes of these mutant mice, as Dab1 protein was absent (yotari) or only barely detectable (scrambler) in these mutants. [26] Targeted disruption of Dab1 also caused a phenotype similar to that of reeler.
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The yotari mouse is an autosomal recessive mutant. [1] It has a mutated disabled homolog 1 ( Dab1 ) gene. [ 2 ] This mutant mouse is recognized by unstable gait ("Yota-ru" in Japanese means "unstable gait") and tremor and by early deaths around the time of weaning .
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