Scrambler, a new neurological mutation of the mouse with abnormalities of neuronal migration

Abstract

A novel spontaneous neurological mutation, scrambler (scm), appeared in the inbred mouse strain DC/Le (dancer) in 1991. Mice homozygous for this recessive mutation are recognized by an unstable gait and whole-body tremor. The cerebella of 30-day-old scrambler homozygotes are hypoplastic and devoid of folia; however, neither seizures nor abnormal brain wave patterns have been observed. Homozygous scrambler mutants have an ataxic gait which in the male may be a contributory factor in the failure to mate. Female homozygotes mate and breed. Life span is not reduced in either sex. Scrambler is similar to the reeler mutation in phenotype and pathology and, like reeler, probably results from defective neuronal migration. We mapped the scrambler mutation to Chromosome (Chr) 4, proving that it is distinct from the recently cloned reeler gene on Chr 5. We also determined the map position of the agrin gene, Agrn, on Chr 4, and on this basis eliminated it as a candidate for scm. Currently there is no known homology of scrambler with human lissencephalies or other human disorders caused by abnormal neuronal migration.

Impaired Neuronal Positioning and Dendritogenesis in the Neocortex after Cell-Autonomous Dab1 Suppression

“…Timed-pregnant Swiss Webster mice were obtained from Taconic Farms (Germantown, NY). scrambler mice were derived from continued inbreeding of a previous outcross of scrambler mice obtained from The Jackson Laboratory (Bar Harbor, ME) (Sweet et al, 1996) to wild-type C57BL/6J. PCR typing of mice.…”

“…We undertook an analysis of the morphology of neurons in explants of the developing scrambler mouse cortex. scrambler mice (Sweet et al, 1996) lack the cytoplasmic adaptor protein Dab1 that is essential for Reelin signaling (Howell et al, 1997b;Sheldon et al, 1997;Ware et al, 1997) yet still express Reelin. Thus, the scrambler cortex presents the opportunity to determine the morphology of Reelininsensitive cells in the presence of Reelin.…”

Mutant mice with scrambled brains: understanding the signaling pathways that control cell positioning in the CNS

“…Shortly after Reln was identified, Davisson and colleagues at the Jackson Laboratory (Bar Harbor, ME) described a reeler-like phenotype in a new spontaneous mouse mutant named scrambler (Sweet et al 1996). These defects were associated with an autosomal recessive mutation that arose in the dancer (DC/Le) strain of mice.…”

Hippocampal dendritic arbor growth in vitro: Regulation by Reelin–Disabled-1 signaling

“…The reeler mouse is a naturally occurring mutant that has been an invaluable tool in identifying crucial components of the Reelin-signaling pathway, which is required for the establishment of the normal brain cytoarchitecture [4,9,10,23,25,29]. The reeler mutation arises in the reelin gene and disrupts expression of Reelin, a large extracellular matrix protein.…”