Mice homozygous for the stumbler spontaneous mutation (stu) have clinical features suggesting a cerebellar defect. They can be recognized at 12 days of age by a stumbling locomotion characterized by a high-stepping broad-based gait. Homozygous mutant mice become less active with age and progressively smaller than their normal sibs and usually die before weaning. There are fewer than normal Purkinje cells and granule cells from about 10 days of age onward and a consequent smaller size of the cerebellum. The Purkinje cells have small dendritic arborizations and immature spines on their somata. They also have an increased number of mitochondrial profiles both in cell bodies and in swellings on dendrites. The morphology of the granule cells appears normal.

Development

The stumbler mutation (stu) arose spontaneously at The Jackson Laboratory in 1975 in the inbred strain C3H/HeJ. It was sibling bred to F32 and was then backcrossed for 2 generations, via backcross-intercross, to C3HeB/FeJ-a/a using ovarian transplantation from homozygous females. To improve breeding performance, the mutation was then backcrossed via ovary transplant into B6C3F1-A^w-J host females mated to C57BL/6J males, followed by intercross of the heterozygous offspring. The strain was continually maintained in this manner of backcross-intercross to C57BL/6J until it was crypreserved in 1992 from matings of C57BL/6J females with heterozygous males at generation N5.

Control Suggestions

Untyped from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

stu

Allele Symbol: stu

Allele Name	stumbler
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	stu, stumbler
Gene Synonym(s)
Strain of Origin	C3H/HeJ
Chromosome	2

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: stu related

Neurobiology Research
- Cerebellar Defects
- Ataxia (Movement) Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: stu/stu
involves: C3H/HeJ * C57BL/6J

growth/size/body region phenotype

decreased body weight
- as early as 9 days of age homozygotes are approximately 15% lighter than controls and by 23 days of age weigh only 40% that of controls

nervous system phenotype

Purkinje cell degeneration
- degenerating Purkinje cells are only seen after 19 days of age

small cerebellum
- after 10 days of age the cerebellum ceases to grow at the same rate as controls, which show rapid cerebellar growth overthe first 3 weeks of life, and thus the stumbler cerebellum is smaller than normal
- the smaller cerebellum is due primarily to a comparative reduction in number of Purkinje cells and granule cells

thin external granule cell layer
- slightly thinner than normal at 10 to 13 days of age

abnormal cerebellar molecular layer

abnormal Purkinje cell morphology
- Purkinje cells have disorganized endoplasmic reticulum and an increased number of mitochondria, although normal-looking synapses are found, and in homozygotes that live to 35 days of age near-normal looking Purkinje cells can be found

abnormal cerebellar cortex morphology
- the length of all of the layers of the cerebellar cortex is shorter than normal

abnormal cerebellar Purkinje cell layer

abnormal Purkinje cell dendrite morphology
- at 9 days of age Purkinje cells have dendritic arborizations that appear immature, are much smaller than normal, and have somatic spines which can still be found at 23 days of age

decreased Purkinje cell number
- Purkinje cells never reach normal numbers

abnormal cerebellar granule layer morphology

thin cerebellar granule layer
- slightly thinner than normal from 10 to 23 days of age, and the volume of the granule layer is reduced in older homozygotes

thin cerebellar molecular layer
- slightly thinner than normal at 10 to 23 days of age

mammalian phenotype

nervous system phenotype
- Normal - the foliation of the cerebellar cortex is normal even though the size is small

Genotype: stu/stu
involves: C3H/HeJ

behavior/neurological phenotype

abnormal gait
- high stepping broad-based gait, stumbling locomotion found by 12 days of age

abnormal righting response
- the righting response is delayed by a day or two so young homozygote have greater than normal difficulty in turning onto their feet

nervous system phenotype

abnormal Purkinje cell differentiation
- cerebeller Purkinje cells fail to mature and have swellings along the larger dendritic trunks, especially at the branch points, and short, spiny dendrites projecting from all parts of the soma
- an increase in the number of mitochondrial profiles in Purkinje cell soma even at 10 days of age
- Purkinje cell nuclei are often eccentrically positioned

abnormal cerebellar granule cell morphology
- some granule cells appear to have longer than normal dendrites
- total number of granule cells is less than normal by 10 days of age

abnormal Purkinje cell morphology
- lings on axons
- Purkinje cells have reduced total volume, irregularly increased caliber, abnormal branching patterns of dendrites, high concentration of mitochondria in soma and dendrites, persistent somatic spines and filopodia at least to 21 days of age, and focal swellings on axons

abnormal Purkinje cell dendrite morphology

decreased Purkinje cell number
- total number of Purkinje cells is less than normal by 10 days of age

small cerebellum
- although smaller than normal, the cerebellum has a normal folial pattern

cellular phenotype

abnormal Purkinje cell differentiation
- Purkinje cell nuclei are often eccentrically positioned
- cerebeller Purkinje cells fail to mature and have swellings along the larger dendritic trunks, especially at the branch points, and short, spiny dendrites projecting from all parts of the soma
- an increase in the number of mitochondrial profiles in Purkinje cell soma even at 10 days of age

growth/size/body region phenotype

decreased body weight
- homozygotes become less active, never gain as much weight as littermate controls, and this weight disparity is progressive

mortality/aging

postnatal lethality
- most homozygotes die before weaning
- Background Sensitivity - on the C3H/HeJ background homozygotes die by 21 days of age, but live slightly longer when crossed with C57BL/6J

References

Additional References

Caddy KW; Sidman RL; Eicher EM. 1981. Stumbler, a new mutant mouse with cerebellar disease. Brain Res 208(1):251-5PubMed: 7470926 MGI: J:6464

Additional - stu related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygous mutant animals die by 18 days on this background (C57BL/6).
- Additional Breeding and Husbandry Support
Citation
When using the stumbler mouse strain in a publication, please cite the originating article(s) and include JAX stock #001772 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
	Progeny testing required but not provided. No genotyping assay is available for these recessive cryo-recovered animals of undefined genotype

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:stumbler

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

stu

Allele Symbol: stu

Disease Terms

Research Areas By Phenotype

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

Genotype: stu related

Mammalian Phenotype Terms by Genotype

Genotype: stu/stuinvolves: C3H/HeJ * C57BL/6J

growth/size/body region phenotype

nervous system phenotype

mammalian phenotype

Genotype: stu/stuinvolves: C3H/HeJ

behavior/neurological phenotype

nervous system phenotype

cellular phenotype

growth/size/body region phenotype

mortality/aging

References

Additional References

Additional - stu related

Genotyping Protocols

Breeding Considerations

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

Genotype: stu/stu
involves: C3H/HeJ * C57BL/6J

Genotype: stu/stu
involves: C3H/HeJ