Description

Strain Information

Type Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain Mixed cross Generation N16 F1p (04-SEP-05)

Description
Mice homozygous for the spastic spontaneous mutation (Glrb^spa) can usually be recognized at 14 days of age but sometimes not until 5 or 6 weeks. They show spastic symptoms which sometimes occur spontaneously and can always be induced by handling. 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 CNS except that herniated intervertebral discs and cysts of the leptomeninges occur, most severely in the lumbar region, possibly as a result of traumatic injuries consequent on spasticity and tremor. 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. There is a decrease to less than 20% of normal in the receptor for glycine, the major inhibitory neurotransmitter in the spinal cord and brainstem.

Development
The spastic mutation (Glrb^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. Breeding stock was received from Dr. Chai in 1963 and after 2 sibling matings Glrb^spa was backcrossed to C57BL/6J to N5. Sibling matings were again made for 12 generations on one line while a second line had 4 generations plus another cross to C57BL/6J followed with 4 more sibling matings. A cross was then done between the two lines and the progeny were sibling mated for 5 generations before maintaining the strain by backcross-intercross to C57BL/6J. In 1985 this strain reached N25. In 1980 N16 embryos were cryopreserved.

Related Strains

Strains carrying   Glrb^spa allele

000241

B6C3Fe a/a-Glrbspa/J

View Strains carrying   Glrb^spa     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

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).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Glrb^spa/Glrb⁺

        B6C3Fe a/a-Glrb^spa/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

Glrb^spa/Glrb^spa

        B6C3Fe a/a-Glrb^spa/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

Glrb^spa/Glrb^spa

        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 anterior 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

View Research Applications

Research Applications

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

Glrb^spa 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]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

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]

Glrb^spa related

Becker 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 (Lond) 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

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery of Strains Needing Progeny Testing. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two untested males and two untested females (two pairs) will be recovered, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the overall recovery time to approximately 25 weeks. However, all pups recovered will be sent. Progeny testing is required to identify the genotype of mice of this strain, as a genotyping assay is not available. This type of testing involves breeding the recovered animals and assessing the phenotype of the offspring in order to identify animals carrying the mutation of interest. We can perform the progeny testing for you as a service or we can ship all recovered animals (at least two untested pairs) to you for progeny testing at your facility. If you perform the progeny testing, there is NO guarantee that a carrier will be identified. If we perform progeny testing as a service, additional breeding time will be required. In this case, when a male and female (one pair) are identified that carry the mutation, they and their offspring will be shipped. Delivery time for strains requiring progeny testing often exceeds 25 weeks and may take 12 months or more due to the difficulties in breeding some strains. The progeny testing cost is in addition to the recovery cost and is based on the number of boxes used and the time taken to produce the mice identified as carrying the mutation. Please note that identified pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Please contact Customer Service for more information on the cost of progeny testing for a strain: Tel: 1-800-422-6423 or 1-207-288-5845. Cryorecovery to establish a Dedicated Supply for greater quantities of mice One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. Genomic DNA is available for this strain from the Mouse DNA Resource.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.