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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Former Names B6C3Fe-a/a-Glrbspa/+ (Changed: 15-DEC-04 ) Type Mutant Stock; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F47pN1 Appearance
black, tremors
Related Genotype: a/a Glrbspa/ Glrbspa
black, unaffected
Related Genotype: a/a +/? or a/a Glrbspa/+Description
Mice homozygous for the spastic spontaneous mutation (Glrbspa) can usually be recognized at 14 days of age, but some mutant mice may not be reliably distinguished until 5 or 6 weeks of age. They show spastic symptoms in response to handling, but spastic behavior can occur spontaneously. The spasms consist of rapid tremor, stiffness of posture, and difficulty in righting when placed on the back. No anatomical pathology occurs in either muscle or the central nervous system, except that herniated intervertebral discs and cysts of the leptomeninges occur, most severely in the lumbar region, possibly resulting from traumatic injuries sustained during the myoclonic episodes. The spastic symptoms can be markedly alleviated by intraperitoneal injection of aminooxyacetic acid, an inhibitor of g-aminobutyric acid transaminase (GABA-T), but not by Dilantin or trimethadione. Glycine receptor expression in the CNS of spastic mice is reduced to 20%, or less, of normal.Development
The spastic mutation (spa) arose spontaneously in the early 1960's at The Jackson Laboratory in a hybrid stock belonging to C. F. Chai that was produced by intercrosses of 6 inbred strains: C57BL/6J, C57BR/cd, A/J, BALB/c, LG and SM. This B6C3Fe-a/a stock of spastic was begun in 1973 by mating a B6.Cg-spa homozygous female at generation N5F5 to a C3H/Gn-a/a male and intercrossing the offspring. A homozygous female from the intercross was then crossed to a B6C3Fe-a/a F1 male and this stock was maintained through this cross-intercross using B6C3Fe-a/a F1 for the cross. In 1997 embryos were generated for cryopreservation by mating heterozygotes at generation N47.
Control Information
| Control | ||
|---|---|---|
| Untyped from the colony | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Glrbspa allele
000066 B6.Cg-Glrbspa/J View Strains carrying Glrbspa (1 strain)
Phenotype
Phenotype Information
Hyperekplexia, Hereditary - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
assigned by genotype
Glrbspa/Glrb+
B6C3Fe a/a-Glrbspa/J
- reproductive system phenotype
- impaired acrosome reaction (MGI Ref ID J:107699)
- the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type
- impaired fertilization (MGI Ref ID J:107699)
- in mutants, the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type
Glrbspa/Glrbspa
B6C3Fe a/a-Glrbspa/J
- reproductive system phenotype
- impaired acrosome reaction (MGI Ref ID J:107699)
- the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type
- impaired fertilization (MGI Ref ID J:107699)
- in mutants, the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Glrbspa/Glrbspa
Background Not Specified
- lethality-postnatal
- postnatal lethality (MGI Ref ID J:13079)
- percentage of mortality is high before or around weaning, although some can live almost a normal life span
- muscle phenotype
- muscle spasm (MGI Ref ID J:13079)
- sudden disturbance or handling causes spasms in which the back is stiff and arched, the legs are stiff and stretched, and the toes are extended
- when held by their tails, backs become stiff and bodies and legs quiver with a high frequency of vibration
- suffer from periods of spasticity which vary in length from one to several minutes; they walk in short steps, on tip-toe and arch their backs
- spasticity is induced by sudden handling
- mutants are recognizeable by 14 days of age
- behavior/neurological phenotype
- abnormal gait (MGI Ref ID J:13079)
- walk on tip-toe during a stimulus-induced spasm
- abnormal maternal nurturing (MGI Ref ID J:13079)
- females produce young but are poor mothers, possibly because of physical difficulties
- abnormal posture (MGI Ref ID J:13079)
- in severe cases of spasms, mutants are arch-backed and slide on the table
- hyperekplexia (MGI Ref ID J:33924)
- impaired righting response (MGI Ref ID J:13079)
- during a spasm, have great difficulty in turning over after being laid on the table with the belly facing upward
- impaired swimming (MGI Ref ID J:13079)
- lack facility in swimming
- increased startle reflex (MGI Ref ID J:33924)
- exhibit increased startle responses to acoustic stimuli of different intensities
- short stride length (MGI Ref ID J:13079)
- walk in short steps during a stimulus-induced spasm
- tremors (MGI Ref ID J:5196)
- when lifted up by the tail, backs stiffen and the entire body and legs quiver violently, indicating tremor
- reproductive system phenotype
- reduced male fertility (MGI Ref ID J:13079)
- frequency of litters from abnormal males is much lower
- hearing/vestibular/ear phenotype
- hyperekplexia (MGI Ref ID J:33924)
- increased startle reflex (MGI Ref ID J:33924)
- exhibit increased startle responses to acoustic stimuli of different intensities
- skeleton phenotype
- abnormal vertebral column (MGI Ref ID J:5196)
- vertebral column abnormalities, with the lumbar region most severely affected, that include intervertebral enchondrosis, hyperplasia of fibrocartilage, and intervertebral arthrosis, probably resulting from disc herniations and ossification
- as early as 24 days of age, exhibit formation of leptomeningeal cysts in the vertebral column, usually located medial to spinal nerve roots
- cysts are lined with a single or multiple layer of cuboidal epithelium and filled with a mucoid fluid and cellular debris and are located between the dura and the spinal cord
- the dorsal longitudinal ligament is thinner dorsally than medially
- in older mutants, the mucoid material ossifies and adheres to the spinal meninges
- abnormal intervertebral disk morphology (MGI Ref ID J:5196)
- acute or subacute disc herniations; rupture of the annulus fibrosus leading to extrusion of the nucleus pulposus
- herniations of the nucleus pulposus are always dorsal or dorsolateral rather than medially
- fragile skeleton (MGI Ref ID J:5196)
- skeleton becomes brittle with increasing age
- nervous system phenotype
- abnormal Purkinje cell morphology (MGI Ref ID J:5196)
- occasionally Purkinje cells are lost
- abnormal brain dura mater morphology (MGI Ref ID J:5196)
- as cysts become distended with fluid, the dura is displaced laterally against the wall of the vertebral canal
- abnormal dorsal root ganglion morphology (MGI Ref ID J:5196)
- necrobiotic changes involve the neurons of the spinal ganglia with certain of these calcifying and many have eccentric nuclei
- abnormal spinal cord morphology (MGI Ref ID J:5196)
- disc protrusions indent the ventral aspects of the spinal cord; indentations are often deep enough to alter the normal shape and symmetry of the spinal cord both in the white and grey matter
- white matter atrophies at the sites of compression
- abnormal spinal cord ventral horn morphology (MGI Ref ID J:5196)
- ventral horn neurons become flattened or stretched due to the compression of the spinal cord and undergo degenerative changes, such as shrinkage, vacuolation, and necrobiosis
- abnormal spinal nerve morphology (MGI Ref ID J:5196)
- compression of the spinal roots by leptomeningeal cysts, leading to impingment of spinal root axons
- nerve fiber myelin and axonal changes occur in spinal roots, spinal nerves, cauda equina, and sciatic nerves
- cardiovascular system phenotype
- hemorrhage (MGI Ref ID J:5196)
- disk herniations cause hemorrhage
- endocrine/exocrine gland phenotype
- abnormal adrenal cortex morphology (MGI Ref ID J:5196)
- adrenal corticism is more evident in older mutants, beginning at about 2 months of age
- enlarged adrenal glands (MGI Ref ID J:5196)
- enlarged due to cortical hypertrophy and hyperplasia
- growth/size phenotype
- decreased body size (MGI Ref ID J:5196)
- homeostasis/metabolism phenotype
- edema (MGI Ref ID J:5196)
- disc herniations cause edema
This mouse can be used to support research in many areas including:Glrbspa related
Cell Biology Research
Channel and Transporter Defects
chloride: glycine receptor
Neurobiology Research
Channel and Transporter Defects
chloride: glycine receptor
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects
Tremor Defects
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Glrbspa | ||
|---|---|---|---|
| Allele Name | spastic | ||
| Allele Type | Spontaneous | ||
| Common Name(s) | spa; | ||
| Gene Symbol and Name | Glrb, glycine receptor, beta subunit | ||
| Chromosome | 3 | ||
| Gene Common Name(s) | AI853901; expressed sequence AI853901; spa; spastic; | ||
| Molecular Note | The mutation in the spastic mouse is an insertion of a 7.1 kilobase LINE-1 element within intron 6 of the gene. Glrb mRNA is markedly reduced throughout brains of homozygous mice, and was shown to be aberrantly spliced. [MGI Ref ID J:18530] [MGI Ref ID J:21071] | ||
| Allele Symbol | a | ||
| Allele Name | nonagouti | ||
| Allele Type | Spontaneous | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Genotyping resources and troubleshooting
References
References
Additional References
Kingsmore SF; Giros B; Suh D; Bieniarz M; Caron MG; Seldin MF. 1994. Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet 7(2):136-41. [PubMed: 7920630] [MGI Ref ID J:18530]
Glrbspa relatedBecker CM; Schmieden V; Tarroni P; Strasser U; Betz H. 1992. Isoform-selective deficit of glycine receptors in the mouse mutant spastic. Neuron 8(2):283-9. [PubMed: 1371219] [MGI Ref ID J:1965]
Becker L; Hartenstein B; Schenkel J; Kuhse J; Betz H; Weiher H. 2000. Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor beta-subunit: an animal model of startle disease. Eur J Neurosci 12(1):27-32. [PubMed: 10651857] [MGI Ref ID J:60037]
CHAI CK; ROBERTS E; SIDMAN RL. 1962. Influence of aminooxyacetic acid, a gamma-aminobutyrate transaminase inhibitor, on hereditary spastic defect in the mouse. Proc Soc Exp Biol Med 109:491-5. [PubMed: 13877851] [MGI Ref ID J:13135]
Chai CK. 1961. Hereditary spasticity in mice. J Hered 52:241-243. [MGI Ref ID J:13079]
Cosgrove AP; Graham HK. 1994. Botulinum toxin A prevents the development of contractures in the hereditary spastic mouse. Dev Med Child Neurol 36(5):379-85. [PubMed: 8168656] [MGI Ref ID J:19062]
Graham BA; Schofield PR; Sah P; Callister RJ. 2003. Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice. J Physiol 551(Pt 3):905-16. [PubMed: 12837931] [MGI Ref ID J:105485]
Graham BA; Schofield PR; Sah P; Margrie TW; Callister RJ. 2006. Distinct physiological mechanisms underlie altered glycinergic synaptic transmission in the murine mutants spastic, spasmodic, and oscillator. J Neurosci 26(18):4880-90. [PubMed: 16672662] [MGI Ref ID J:108318]
Handford CA; Lynch JW; Baker E; Webb GC; Ford JH; Sutherland GR; Schofield PR. 1996. The human glycine receptor beta subunit: primary structure, functional characterisation and chromosomal localisation of the human and murine genes. Brain Res Mol Brain Res 35(1-2):211-9. [PubMed: 8717357] [MGI Ref ID J:31284]
Hartenstein B; Schenkel J; Kuhse J; Besenbeck B; Kling C; Becker CM; Betz H; Weiher H. 1996. Low level expression of glycine receptor beta subunit transgene is sufficient for phenotype correction in spastic mice. EMBO J 15(6):1275-82. [PubMed: 8635460] [MGI Ref ID J:32212]
Kingsmore SF; Giros B; Suh D; Bieniarz M; Caron MG; Seldin MF. 1994. Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet 7(2):136-41. [PubMed: 7920630] [MGI Ref ID J:18530]
Koch M; Kling C; Becker CM. 1996. Increased startle responses in mice carrying mutations of glycine receptor subunit genes. Neuroreport 7(3):806-8. [PubMed: 8733750] [MGI Ref ID J:33924]
Meier H; Chai CK. 1970. Spastic, an hereditary neurological mutation in the mouse characterized by vertebral arthropathy and leptomeningeal cyst formation. Exp Med Surg 28(1):24-38. [PubMed: 4323808] [MGI Ref ID J:5196]
Molon A; Di Giovanni S; Hathout Y; Natale J; Hoffman EP. 2006. Functional recovery of glycine receptors in spastic murine model of startle disease. Neurobiol Dis 21(2):291-304. [PubMed: 16182553] [MGI Ref ID J:105777]
Mulhardt C; Fischer M; Gass P; Simon-Chazottes D; Guenet JL; Kuhse J; Betz H; Becker CM. 1994. The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element. Neuron 13(4):1003-15. [PubMed: 7946325] [MGI Ref ID J:21071]
Muller E; Le Corronc H; Scain AL; Triller A; Legendre P. 2008. Despite GABAergic neurotransmission, GABAergic innervation does not compensate for the defect in glycine receptor postsynaptic aggregation in spastic mice. Eur J Neurosci 27(10):2529-41. [PubMed: 18445051] [MGI Ref ID J:136684]
Pinto LH; Grunert U; Studholme K; Yazulla S; Kirsch J; Becker CM. 1994. Glycine receptors in the retinas of normal and spastic mutant mice. Invest Ophthalmol Vis Sci 35(10):3633-9. [PubMed: 8088953] [MGI Ref ID J:21161]
Roberts E; Kuriyama K. 1968. Biochemical-physiological correlations in studies of the gamma-aminobutyric acid system. Brain Res 8(1):1-35. [PubMed: 4870412] [MGI Ref ID J:5069]
Sato Y; Son JH; Tucker RP; Meizel S. 2000. The zona pellucida-initiated acrosome reaction: defect due to mutations in the sperm glycine receptor/Cl(-) channel. Dev Biol 227(1):211-8. [PubMed: 11076688] [MGI Ref ID J:107699]
Shiang R; Ryan SG; Zhu YZ; Hahn AF; O'Connell P; Wasmuth JJ. 1993. Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet 5(4):351-8. [PubMed: 8298642] [MGI Ref ID J:20117]
Simon ES. 1997. Phenotypic heterogeneity and disease course in three murine strains with mutations in genes encoding for alpha 1 and beta glycine receptor subunits. Mov Disord 12(2):221-8. [PubMed: 9087981] [MGI Ref ID J:41909]
Stone C; Pinto LH. 1992. Receptive field organization of retinal ganglion cells in the spastic mutant mouse. J Physiol 456:125-42. [PubMed: 1338094] [MGI Ref ID J:797]
White WF. 1985. The glycine receptor in the mutant mouse spastic (spa): strychnine binding characteristics and pharmacology. Brain Res 329(1-2):1-6. [PubMed: 2983837] [MGI Ref ID J:7776]
White WF; Heller AH. 1982. Glycine receptor alteration in the mutant mouse spastic. Nature 298(5875):655-7. [PubMed: 6285205] [MGI Ref ID J:6816]
Yazulla S; Studholme KM; Pinto LH. 1997. Differences in the retinal GABA system among control, spastic mutant and retinal degeneration mutant mice. Vision Res 37(24):3471-82. [PubMed: 9425524] [MGI Ref ID J:45280]
von Wegerer J; Becker K; Glockenhammer D; Becker CM; Zeilhofer HU; Swandulla D. 2003. Spinal inhibitory synaptic transmission in the glycine receptor mouse mutant spastic. Neurosci Lett 345(1):45-8. [PubMed: 12809985] [MGI Ref ID J:107528]
Health & husbandry
Health & Colony Maintenance Information
Currently there no information available for this strain. This may be due to the supply level of this strain.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
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Supply Details
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Untyped from the colony | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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See Terms of Use tab for General Terms and Conditions
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.Ordering and Purchasing Information
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