Scrambler mouse: Difference between revisions
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==Neuroanatomical abnormalities== |
==Neuroanatomical abnormalities== |
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The spontaneous [[autosomal]] [[recessive]] scrambler mutation on [[chromosome 4]] causes a deficiency of disabled-1, a protein involved in the signaling of the reelin protein, lacking in the reeler mutant, <ref>Rice DS, Sheldon M, D'Arcangelo G, Nakajima K, Goldowitz D, Curran T. Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain. Development 125, 3719-29, 1998, PMID 9716537</ref> Dba1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in cerebellar cortex, hippocampus, and neocortex. <ref>Sheldon M, Rice DS, D'Arcangelo G, Yoneshima H, Nakajima K, Mikoshiba K, Howell BW, Cooper JA, Goldowitz D, Curran T. Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice. Nature 389, 730-3, 1997, PMID 11784791</ref><ref>Weiss KH, Johanssen C, Tielsch A, Herz J, Deller T, Frotscher M, Förster E. Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR-deficient mice. J Comp Neurol 460, 56-65, 2003, PMID 12687696.</ref> [[Purkinje cell]] and [[granule cell]] degeneration results in [[ataxia]].<ref> Goldowitz D, Cushing RC, Laywell E, D'Arcangelo G, Sheldon M, Sweet HO, Davisson M, Steindler D, Curran T. Cerebellar disorganization characteristic of reeler in scrambler mutant mice despite presence of reelin. J Neurosci 17: 8767-77, 1997, PMID 9348346</ref> 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. <ref>Gallagher E, Howell BW, Soriano P, Cooper JA, Hawkes R. Cerebellar abnormalities in the disabled (mdab1-1) mouse. J Comp Neurol 402, 238-51, 1998, PMID 9845246</ref> <ref> Howell BW, Hawkes R, Soriano P, Cooper JA. Neuronal position in the developing brain is regulated by mouse disabled-1. Nature 389, 733-7, 1997, PMID 9338785</ref> |
The spontaneous [[autosomal]] [[recessive]] scrambler mutation on [[chromosome 4]] causes a deficiency of disabled-1, a protein involved in the signaling of the reelin protein, lacking in the reeler mutant, <ref>Rice DS, Sheldon M, D'Arcangelo G, Nakajima K, Goldowitz D, Curran T. Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain. Development 125, 3719-29, 1998, PMID 9716537</ref> Dba1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in cerebellar cortex, hippocampus, and neocortex. <ref>Sheldon M, Rice DS, D'Arcangelo G, Yoneshima H, Nakajima K, Mikoshiba K, Howell BW, Cooper JA, Goldowitz D, Curran T. Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice. Nature 389, 730-3, 1997, PMID 11784791</ref><ref>Weiss KH, Johanssen C, Tielsch A, Herz J, Deller T, Frotscher M, Förster E. Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR-deficient mice. J Comp Neurol 460, 56-65, 2003, PMID 12687696.</ref> [[Purkinje cell]] and [[granule cell]] degeneration results in [[ataxia]].<ref> Goldowitz D, Cushing RC, Laywell E, D'Arcangelo G, Sheldon M, Sweet HO, Davisson M, Steindler D, Curran T. Cerebellar disorganization characteristic of reeler in scrambler mutant mice despite presence of reelin. J Neurosci 17: 8767-77, 1997, PMID 9348346</ref> 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. <ref>Gallagher E, Howell BW, Soriano P, Cooper JA, Hawkes R. Cerebellar abnormalities in the disabled (mdab1-1) mouse. J Comp Neurol 402, 238-51, 1998, PMID 9845246</ref> <ref> Howell BW, Hawkes R, Soriano P, Cooper JA. Neuronal position in the developing brain is regulated by mouse disabled-1. Nature 389, 733-7, 1997, PMID 9338785</ref> |
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==Behavioral abnormalities]] |
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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.<ref>Lalonde R, Strazielle C. Sensorimotor learning in Dab1(scm) (scrambler) mutant mice. Behav Brain Res 218, 350-2, 2011, PMID 21167868 </ref> |
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==References== |
==References== |
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Revision as of 14:27, 2 March 2011
Scrambler is a spontaneous mutant lacking a functional DAB1 gene, resulting in a phenotype resembling that seen in the Reeler mouse.[1] The strain was first described by Sweet et al in 1996.[2]
Neuroanatomical abnormalities
The spontaneous autosomal recessive scrambler mutation on chromosome 4 causes a deficiency of disabled-1, a protein involved in the signaling of the reelin protein, lacking in the reeler mutant, [3] Dba1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in cerebellar cortex, hippocampus, and neocortex. [4][5] Purkinje cell and granule cell degeneration results in ataxia.[6] 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. [7] [8]
==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.[9]
References
- ^ González JL, Russo CJ, Goldowitz D, Sweet HO, Davisson MT, Walsh CA. Birthdate and cell marker analysis of scrambler: a novel mutation affecting cortical development with a reeler-like phenotype. J. Neurosci. 17, 9204–11, 1997, PMID 9364067, http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=9364067
- ^ Sweet HO, Bronson RT, Johnson KR, Cook SA, Davisson MT |title=Scrambler, a new neurological mutation of the mouse with abnormalities of neuronal migration. Mamm. Genome 7, 798–802, 1996, PMID 8875886, http://link.springer-ny.com/link/service/journals/00335/bibs/7n11p798.html}}
- ^ Rice DS, Sheldon M, D'Arcangelo G, Nakajima K, Goldowitz D, Curran T. Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain. Development 125, 3719-29, 1998, PMID 9716537
- ^ Sheldon M, Rice DS, D'Arcangelo G, Yoneshima H, Nakajima K, Mikoshiba K, Howell BW, Cooper JA, Goldowitz D, Curran T. Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice. Nature 389, 730-3, 1997, PMID 11784791
- ^ Weiss KH, Johanssen C, Tielsch A, Herz J, Deller T, Frotscher M, Förster E. Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR-deficient mice. J Comp Neurol 460, 56-65, 2003, PMID 12687696.
- ^ Goldowitz D, Cushing RC, Laywell E, D'Arcangelo G, Sheldon M, Sweet HO, Davisson M, Steindler D, Curran T. Cerebellar disorganization characteristic of reeler in scrambler mutant mice despite presence of reelin. J Neurosci 17: 8767-77, 1997, PMID 9348346
- ^ Gallagher E, Howell BW, Soriano P, Cooper JA, Hawkes R. Cerebellar abnormalities in the disabled (mdab1-1) mouse. J Comp Neurol 402, 238-51, 1998, PMID 9845246
- ^ Howell BW, Hawkes R, Soriano P, Cooper JA. Neuronal position in the developing brain is regulated by mouse disabled-1. Nature 389, 733-7, 1997, PMID 9338785
- ^ Lalonde R, Strazielle C. Sensorimotor learning in Dab1(scm) (scrambler) mutant mice. Behav Brain Res 218, 350-2, 2011, PMID 21167868