Overview

Also Known As:spastic

Mice homozygous for the spastic spontaneous mutation (Glrb^spa) 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.

Genetic overview

Genetic Background	Generation

Glrb^spa

Allele Type	Gene Symbol	Gene Name
Spontaneous	Glrb	glycine receptor, beta subunit

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

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Research Applications

Neurobiology Research
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the spastic spontaneous mutation (Glrb^spa) 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 Suggestions

Untyped from the colony

Additional Information

Considerations for Choosing Controls

Genetics

Glrb^spa

Allele Symbol: Glrb^spa

Allele Name	spastic
Allele Type	Spontaneous
Allele Synonym(s)	spa
Gene Symbol and Name	Glrb, glycine receptor, beta subunit
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	3
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.

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
General Note	Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039
Molecular Note	Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

hyperekplexia 2

Research Areas By Phenotype

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

Genotype: Glrb^spa related

Neurobiology Research
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Receptor Defects
- Tremor Defects
- Channel and Transporter Defects
  - chloride: glycine receptor
  - chloride
Cell Biology Research
- Channel and Transporter Defects
  - chloride: glycine receptor
  - chloride

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Glrb^spa/Glrb^spa
Not Specified

behavior/neurological phenotype

abnormal gait
- walk on tip-toe during a stimulus-induced spasm

abnormal maternal nurturing
- females produce young but are poor mothers, possibly because of physical difficulties

abnormal posture
- in severe cases of spasms, mutants are arch-backed and slide on the table

hyperekplexia

impaired righting response
- during a spasm, have great difficulty in turning over after being laid on the table with the belly facing upward

impaired swimming
- lack facility in swimming

increased startle reflex
- exhibit increased startle responses to acoustic stimuli of different intensities

short stride length
- walk in short steps during a stimulus-induced spasm

tremors
- when lifted up by the tail, backs stiffen and the entire body and legs quiver violently, indicating tremor

cardiovascular system phenotype

hemorrhage
- disk herniations cause hemorrhage

endocrine/exocrine gland phenotype

abnormal adrenal cortex morphology
- adrenal corticism is more evident in older mutants, beginning at about 2 months of age

enlarged adrenal glands
- enlarged due to cortical hypertrophy and hyperplasia

growth/size/body region phenotype

decreased body size

homeostasis/metabolism phenotype

edema
- disc herniations cause edema

mortality/aging

postnatal lethality, incomplete penetrance
- percentage of mortality is high before or around weaning, although some can live almost a normal life span

muscle phenotype

muscle spasm
- mutants are recognizeable by 14 days of age
- spasticity is induced by sudden handling
- 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
- 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
- when held by their tails, backs become stiff and bodies and legs quiver with a high frequency of vibration

nervous system phenotype

abnormal brain dura mater morphology
- as cysts become distended with fluid, the dura is displaced laterally against the wall of the vertebral canal

abnormal dorsal root ganglion morphology
- necrobiotic changes involve the neurons of the spinal ganglia with certain of these calcifying and many have eccentric nuclei

abnormal Purkinje cell morphology
- occasionally Purkinje cells are lost

abnormal spinal cord morphology
- 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
- 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
- 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

reproductive system phenotype

reduced male fertility
- frequency of litters from abnormal males is much lower

skeleton phenotype

abnormal intervertebral disk morphology
- 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

abnormal vertebral column morphology
- 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
- in older mutants, the mucoid material ossifies and adheres to the spinal meninges
- the dorsal longitudinal ligament is thinner dorsally than medially
- 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

fragile skeleton
- skeleton becomes brittle with increasing age

The following phenotype relates to a compound genotype created using this strain

Genotype: Glrb^spa/Glrb^spa
B6C3Fe a/a-Glrb/J

cellular phenotype

impaired acrosome reaction
- the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type

reproductive system phenotype

impaired acrosome reaction
- the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type

impaired fertilization
- in mutants, the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type

Genotype: Glrb^spa/Glrb⁺
B6C3Fe a/a-Glrb/J

cellular phenotype

impaired acrosome reaction
- the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type

reproductive system phenotype

impaired acrosome reaction
- the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type

impaired fertilization
- in mutants, the zona pellucida-initiated acrosome reaction is significantly decreased compared to wild-type

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):136-41PubMed: 7920630 MGI: J:18530

Additional - a related

Additional - Glrb^spa related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Glrb
- Genotyping resources and troubleshooting
Appearance
- black, tremors
  Related Genotype: a/a Glrb^spa/ Glrb^spa
  
  black, unaffected
  Related Genotype: a/a +/? or a/a Glrb^spa/+
Citation
When using the spastic mouse strain in a publication, please cite the originating article(s) and include JAX stock #000241 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for a, Heterozygous or Homozygous or Wild-type for Glrb<spa>

Payment Terms and Conditions

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

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Licensing Information

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JAX® Mice, Products & Services Conditions of Use

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Also Known As:spastic

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Glrbspa

Allele Symbol: Glrbspa

a

Allele Symbol: a

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Genotype: Glrbspa related

Mammalian Phenotype Terms by Genotype

Genotype: Glrbspa/GlrbspaNot Specified

behavior/neurological phenotype

cardiovascular system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

mortality/aging

muscle phenotype

nervous system phenotype

reproductive system phenotype

skeleton phenotype

Genotype: Glrbspa/GlrbspaB6C3Fe a/a-Glrb/J

cellular phenotype

reproductive system phenotype

Genotype: Glrbspa/Glrb+B6C3Fe a/a-Glrb/J

cellular phenotype

reproductive system phenotype

References

Additional References

Additional - a related

Additional - Glrbspa related

Genotyping Protocols

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Glrb^spa

Allele Symbol: Glrb^spa

Genotype: Glrb^spa related

Genotype: Glrb^spa/Glrb^spa
Not Specified

Genotype: Glrb^spa/Glrb^spa
B6C3Fe a/a-Glrb/J

Genotype: Glrb^spa/Glrb⁺
B6C3Fe a/a-Glrb/J

Additional - Glrb^spa related