Description

Strain Information

Type Mutant Stock; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System TJL Breeding Summary: homozygote x untyped sibling (+/?) then heterozygote x heterozygote. Species laboratory mouse Generation N1F34 (25-JUL-12) Generation Definitions

Appearance
agouti, ataxic
Related Genotype: A/A Dab1^scm/Dab1^scm

agouti, unaffected
Related Genotype: A/A Dab1^scm/Dab1^scm or A/A +/?

Description
Mice homozygous for the scrambler spontaneous mutation (Dab1^scm) 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. Scrambler is similar to the reeler mutation in phenotype and pathology and, like reeler, probably results from defective neuronal migration. Female homozygotes mate and breed. Homozygous scrambler mutants have an ataxic gait which in the male may be contributory factor in the failure to mate. Normal life span for both sexes.

Control Information

	Control
	+/? from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Dab1

006408	B6.Cg-Dab1scm-3J/J
010970	CBA/J-Dab1scm-4J/GrsrJ
003581	CBy.129S4-Dab1tm1Cpr/J
003925	MRL(Cg)-Dab1scm-2J/J

View Strains carrying other alleles of Dab1     (4 strains)

Additional Web Information

JAX^® NOTES, Summer 2007; 506. JAX^® In Vivo Services Drug Efficacy Studies: Sample Morris Water Maze Study.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Dab1^scm/Dab1^scm

        involves: C3HeB/FeJ * DC/Le

• mortality/aging
• decreased survivor rate
  • mice that do survive live a normal lifespan   (MGI Ref ID J:37166)
• postnatal lethality
  • unless litters are culled to reduce competition for food, a significant number of mutants die before weaning   (MGI Ref ID J:37166)
• growth/size phenotype
• decreased body size
  • size difference begins to show after 15 days of age   (MGI Ref ID J:37166)
  • mutant mice frequently cannot be weaned until 5-6 weeks of age; culling some normal siblings prior to weaning can assure survivability of mutant mice   (MGI Ref ID J:37166)
• behavior/neurological phenotype
• abnormal gait   (MGI Ref ID J:37166)
• abnormal motor coordination/ balance
  • phenotype is consistent throughout life   (MGI Ref ID J:37166)
• tremors
  • mice exhibit a whole-body tremor   (MGI Ref ID J:37166)
• reproductive system phenotype
• male infertility   (MGI Ref ID J:37166)
• nervous system phenotype
• abnormal cerebellar Purkinje cell layer
  • a layer is not seen; Purkinje cells are scattered throughout the granule layer and beneath it   (MGI Ref ID J:37166)
• abnormal cerebellar foliation
  • this layer is not seen or reduced   (MGI Ref ID J:37166)
• abnormal cerebral cortex morphology
  • this area lacks its normal six layered structure   (MGI Ref ID J:37166)
  • large pyramidal cells and small granule cells are scattered rather than segregated into specific layers   (MGI Ref ID J:37166)
• • abnormal stratification in cerebral cortex   (MGI Ref ID J:37166)
• abnormal hippocampus morphology
  • this area is severely disorganized   (MGI Ref ID J:37166)
  • the pyramidal cells are aligned in two or more wavy rows rather than in a single curving row   (MGI Ref ID J:37166)
• • abnormal dentate gyrus morphology
    • neurons are randomly scattered   (MGI Ref ID J:37166)
  • abnormal hippocampus pyramidal cell morphology   (MGI Ref ID J:37166)
• small cerebellum
  • greatly reduced in size compared with normal littermates   (MGI Ref ID J:37166)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Dab1^scm/Dab1^scm

        involves: C3H * C57BL/6J

• nervous system phenotype
• abnormal retinal rod bipolar cell morphology
  • density of cells is decreased, indicating a decreased number of rod bipolar cells compared to controls   (MGI Ref ID J:71970)
• vision/eye phenotype
• abnormal cone electrophysiology
  • cone mediated-responses are reduced in amplitude and delayed in mutants; difference compared to wild-type cone function is not as great as differences in rod function   (MGI Ref ID J:71970)
• abnormal retinal inner nuclear layer morphology
  • density of synaptic terminals is decreased compared to controls   (MGI Ref ID J:71970)
• abnormal retinal rod bipolar cell morphology
  • density of cells is decreased, indicating a decreased number of rod bipolar cells compared to controls   (MGI Ref ID J:71970)
• abnormal rod electrophysiology
  • amplitude of a-wave of ERG in response to bright light flash is smaller than in controls while the b-wave is significantly reduced   (MGI Ref ID J:71970)
  • oscillatory potentials (OPs) are reduced in amplitude   (MGI Ref ID J:71970)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Dab1^scm related

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects
Cortical Defects
Neurodevelopmental Defects
Tremor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dab1scm
Allele Name		scrambler
Allele Type		Spontaneous
Common Name(s)		scm;
Strain of Origin		DC/LeJ
Gene Symbol and Name		Dab1, disabled 1
Chromosome		4
Gene Common Name(s)		AI956902; C630028C02Rik; RIKEN cDNA C630028C02 gene; expressed sequence AI956902; scm; scr; scrambler; yot; yotari;
Molecular Note		Transcripts produced from this allele show abnormal splicing and are predicted to produce a truncated protein. Sequence analysis revealed that the larger scrambler transcript contains 1.5 kb of intracisternal A particle retrotransposon (IAP) sequence inantisense orientation. Previous mapping studies detcted an IAP particle that failed to recombine with the Dab1 locus. Thus, it appears that abberrant splicing has incorporated the IAP element in the coding region of the gene. [MGI Ref ID J:42628] [MGI Ref ID J:43504]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Sweet HO; Bronson RT; Johnson KR; Cook SA; Davisson MT. 1996. Scrambler, a new neurological mutation of the mouse with abnormalities of neuronal migration. Mamm Genome 7(11):798-802. [PubMed: 8875886]  [MGI Ref ID J:37166]

Ware ML; Fox JW; Gonzalez JL; Davis NM; Lambert de Rouvroit C ; Russo CJ ; Chua SC Jr ; Goffinet AM ; Walsh CA. 1997. Aberrant splicing of a mouse disabled homolog, mdab1, in the scrambler mouse. Neuron 19(2):239-49. [PubMed: 9292716]  [MGI Ref ID J:42628]

Weiss KH; Johanssen C; Tielsch A; Herz J; Deller T; Frotscher M; Forster E. 2003. Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR-deficient mice. J Comp Neurol 460(1):56-65. [PubMed: 12687696]  [MGI Ref ID J:83151]

Dab1^scm related

Akopians AL; Babayan AH; Beffert U; Herz J; Basbaum AI; Phelps PE. 2008. Contribution of the Reelin signaling pathways to nociceptive processing. Eur J Neurosci 27(3):523-37. [PubMed: 18279306]  [MGI Ref ID J:132269]

Borrell V; Pujadas L; Simo S; Dura D; Sole M; Cooper JA; Del Rio JA; Soriano E. 2007. Reelin and mDab1 regulate the development of hippocampal connections. Mol Cell Neurosci 36(2):158-73. [PubMed: 17720534]  [MGI Ref ID J:126745]

Cariboni A; Rakic S; Liapi A; Maggi R; Goffinet A; Parnavelas JG. 2005. Reelin provides an inhibitory signal in the migration of gonadotropin-releasing hormone neurons. Development 132(21):4709-18. [PubMed: 16207762]  [MGI Ref ID J:102848]

Chung S; Zhang Y; Van Der Hoorn F; Hawkes R. 2007. The anatomy of the cerebellar nuclei in the normal and scrambler mouse as revealed by the expression of the microtubule-associated protein kinesin light chain 3. Brain Res 1140:120-31. [PubMed: 17447264]  [MGI Ref ID J:121113]

Chung SH; Sillitoe RV; Croci L; Badaloni A; Consalez G; Hawkes R. 2009. Purkinje cell phenotype restricts the distribution of unipolar brush cells. Neuroscience 164(4):1496-508. [PubMed: 19800947]  [MGI Ref ID J:156632]

David A; Tiveron MC; Defays A; Beclin C; Camosseto V; Gatti E; Cremer H; Pierre P. 2007. BAD-LAMP defines a subset of early endocytic organelles in subpopulations of cortical projection neurons. J Cell Sci 120(Pt 2):353-65. [PubMed: 17215451]  [MGI Ref ID J:117449]

Goldowitz D; Cushing RC; Laywell E; D'Arcangelo G; Sheldon M; Sweet HO; Davisson M; Steindler D; Curran T. 1997. Cerebellar disorganization characteristic of reeler in scrambler mutant mice despite presence of reelin. J Neurosci 17(22):8767-77. [PubMed: 9348346]  [MGI Ref ID J:44084]

Gonzalez JL; Russo CJ; Goldowitz D; Sweet HO; Davisson MT; Walsh CA. 1997. Birthdate and cell marker analysis of scrambler: a novel mutation affecting cortical development with a reeler-like phenotype. J Neurosci 17(23):9204-11. [PubMed: 9364067]  [MGI Ref ID J:44289]

Gupta A; Sanada K; Miyamoto DT; Rovelstad S; Nadarajah B; Pearlman AL; Brunstrom J; Tsai LH. 2003. Layering defect in p35 deficiency is linked to improper neuronal-glial interaction in radial migration. Nat Neurosci 6(12):1284-91. [PubMed: 14608361]  [MGI Ref ID J:86637]

Hashimoto-Torii K; Torii M; Sarkisian MR; Bartley CM; Shen J; Radtke F; Gridley T; Sestan N; Rakic P. 2008. Interaction between Reelin and Notch signaling regulates neuronal migration in the cerebral cortex. Neuron 60(2):273-84. [PubMed: 18957219]  [MGI Ref ID J:144065]

Jacquelin C; Strazielle C; Lalonde R. 2012. Neurologic function during developmental and adult stages in Dab1(scm) (scrambler) mutant mice. Behav Brain Res 226(1):265-73. [PubMed: 21945093]  [MGI Ref ID J:177725]

Jossin Y; Goffinet AM. 2007. Reelin signals through phosphatidylinositol 3-kinase and Akt to control cortical development and through mTor to regulate dendritic growth. Mol Cell Biol 27(20):7113-24. [PubMed: 17698586]  [MGI Ref ID J:126769]

Jossin Y; Gui L; Goffinet AM. 2007. Processing of Reelin by embryonic neurons is important for function in tissue but not in dissociated cultured neurons. J Neurosci 27(16):4243-52. [PubMed: 17442808]  [MGI Ref ID J:121108]

Lalonde R; Strazielle C. 2011. Sensorimotor learning in Dab1(scm) (scrambler) mutant mice. Behav Brain Res 218(2):350-2. [PubMed: 21167868]  [MGI Ref ID J:168610]

Rice DS; Nusinowitz S; Azimi AM; Martinez A; Soriano E; Curran T. 2001. The reelin pathway modulates the structure and function of retinal synaptic circuitry. Neuron 31(6):929-41. [PubMed: 11580894]  [MGI Ref ID J:71970]

Rice DS; Sheldon M; D'Arcangelo G; Nakajima K; Goldowitz D; Curran T. 1998. Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain. Development 125(18):3719-29. [PubMed: 9716537]  [MGI Ref ID J:50400]

Rossel M; Loulier K; Feuillet C; Alonso S; Carroll P. 2005. Reelin signaling is necessary for a specific step in the migration of hindbrain efferent neurons. Development 132(6):1175-85. [PubMed: 15703280]  [MGI Ref ID J:97218]

Sanada K; Gupta A; Tsai LH. 2004. Disabled-1-regulated adhesion of migrating neurons to radial glial fiber contributes to neuronal positioning during early corticogenesis. Neuron 42(2):197-211. [PubMed: 15091337]  [MGI Ref ID J:90026]

Sheldon M; Rice DS; D'Arcangelo G; Yoneshima H; Nakajima K; Mikoshiba K ; Howell BW ; Cooper JA ; Goldowitz D ; Curran T. 1997. Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice [see comments] Nature 389(6652):730-3. [PubMed: 9338784]  [MGI Ref ID J:43504]

Strazielle C; Lefevre A; Jacquelin C; Lalonde R. 2012. Abnormal grooming activity in Dab1(scm) (scrambler) mutant mice. Behav Brain Res 233(1):24-8. [PubMed: 22561124]  [MGI Ref ID J:190502]

Su J; Haner CV; Imbery TE; Brooks JM; Morhardt DR; Gorse K; Guido W; Fox MA. 2011. Reelin is required for class-specific retinogeniculate targeting. J Neurosci 31(2):575-86. [PubMed: 21228166]  [MGI Ref ID J:168228]

Sweet HO; Bronson RT; Johnson KR; Cook SA; Davisson MT. 1996. Scrambler, a new neurological mutation of the mouse with abnormalities of neuronal migration. Mamm Genome 7(11):798-802. [PubMed: 8875886]  [MGI Ref ID J:37166]

Ware ML; Fox JW; Gonzalez JL; Davis NM; Lambert de Rouvroit C ; Russo CJ ; Chua SC Jr ; Goffinet AM ; Walsh CA. 1997. Aberrant splicing of a mouse disabled homolog, mdab1, in the scrambler mouse. Neuron 19(2):239-49. [PubMed: 9292716]  [MGI Ref ID J:42628]

Weiss KH; Johanssen C; Tielsch A; Herz J; Deller T; Frotscher M; Forster E. 2003. Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR-deficient mice. J Comp Neurol 460(1):56-65. [PubMed: 12687696]  [MGI Ref ID J:83151]

Yang H; Jensen P; Goldowitz D. 2002. The community effect and Purkinje cell migration in the cerebellar cortex: analysis of scrambler chimeric mice. J Neurosci 22(2):464-70. [PubMed: 11784791]  [MGI Ref ID J:73748]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	Comments: homozygotes should not be weaned until 5-6 weeks of age. Homozygous males do not breed.
Mating System	TJL Breeding Summary: homozygote x untyped sibling (+/?) then heterozygote x heterozygote.
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• View the complete collection of spontaneous mutants in the Mouse Mutant Resource.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	+/? from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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