Overview

Also Known As:megencephaly

These mice carry a spontaneous mutation (megencephaly) at the Kcna1 locus characterized by increase in brain size that is different from macrocephaly.

Genetic overview

Genetic Background	Generation

Kcna1^mceph

Allele Type	Gene Symbol	Gene Name
Spontaneous	Kcna1	potassium voltage-gated channel, shaker-related subfamily, member 1

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Research Applications

Neurobiology Research
Developmental 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 megencephaly spontaneous mutation (Kcna1^mceph) are characterized by a 25% increase in brain size in the first 8 months of life. This defect can be distinguished from macrocephaly, an enlarged head, which usually occurs as a consequence of congenital hydrocephalus. By 3-4 weeks of age, mice homozygous for the mceph mutation have a subtle shakiness in their gate and by 4-6 weeks are found to sit on their haunches using their tails as support with their forelimbs held loosely in front of them. They maintain this posture for a period ranging from 30 seconds to several minutes before returning to normal. They have lower overall body weights than their wildtype littermates and are hypersensitive to sharp sounds. Electroencephalogram readings for homozygotes are normal. Neither male nor female mutants breed, but ovarian transplant from homozygous donors is successful for colony maintenance. Homozygotes have an increased brain mass that is evident by one to two months of age and increases at least until 10 weeks of age, possibly longer. Hypertrophic astrocytes in the hippocampus were the only lesion detected by electron microscopy. This increase in brain mass does not appear to result from edema, hydrocephalus, or an increase in size restricted to any specific area of the brain. The ventricles were not found to be dilated, and no apparent increase in myelin was found. Two month old homozygotes did not show BrdU uptake in brain tissue, and the protein:DNA ration was normal. Thus, mceph appears to cause overall hypertrophy of cells in the brain rather than hyperplasia. Brains from homozygotes have only 13.8% fat while wild type have 15.6% fat.

In several evolutionarily associated regions of the brain, Petersson et al. found co-localized increases in mRNA levels for transforming growth factor beta 1, and insulin-like growth factor binding proteins 2, 4, 5, and 6 with decreases in mRNA levels for Insulin-like growth factor binding protein 5. These imbalances were found in the cerebral cortex, hippocampus, amygdala, and piriform/entorhinal cortex of homozygotes. They also reported a decreased transcript level in the corpus callosum for proteolipid protein of myelin. Immunohistochemistry and in situ hybridization also revealed changes in the expression levels of enkephalin, galanin, neuropeptide Y, and cholecystokinin in specific regions of the hippocampal formation and in ventral cortices. (Petersson et al., 1999; Peterson et al., 2000.)

Megencephaly occurs in several acquired and inherited human diseases including Sotos syndrome, Robinow syndrome, Canavan's disease, and Alexander disease.

Development

The mceph mutation arose spontaneously on the BALB/cByJ inbred background at The Jackson Laboratory in 1983. It was maintained primarily via a backcross-intercross breeding scheme in which the backcross used a BALB/cByJ male bred to a host female transplanted with ovarian tissue from a homozygous female. Attempts to freeze embryos on the pure BALB/cByJ background were not adequately successful. Thus, this strain was frozen in 1995 by breeding C57BL/6J females to heterozygous BALB/cByJ-mceph males. Thus the embryos are heterozygous or wildtype F1.

Control Suggestions

Untyped from the colony

Additional Information

Considerations for Choosing Controls

Genetics

Kcna1^mceph

Allele Symbol: Kcna1^mceph

Allele Name	megencephaly
Allele Type	Spontaneous
Allele Synonym(s)	Kv1.1^mceph; mceph
Gene Symbol and Name	Kcna1, potassium voltage-gated channel, shaker-related subfamily, member 1
Gene Synonym(s)
Strain of Origin	BALB/cByJ
Chromosome	6
Molecular Note	An 11 bp deletion occurs in this mutant, either between bp 2124 and 2134 or between 2129 and 2139. This deletion causes a frame shift which creates a premature stop codon. The resulting protein is 230 amino acids in length as opposed to 495 amino acids for a normal protein. The cytosolic N-terminal, first transmembrane segment and extracellular loop of the protein are preserved.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Kcna1^mceph related

Neurobiology Research
- Neurodevelopmental Defects
Developmental Biology Research
- Internal/Organ Defects
  - brain

Mammalian Phenotype Terms by Genotype

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

Genotype: Kcna1^mceph/Kcna1^mceph
BALB/cByJ-Kcna1/J

behavior/neurological phenotype

abnormal gait
- subtle shakiness of gait

abnormal locomotor behavior
- abnormal limb paddling

abnormal posture
- by 4-6 weeks of age homozygotes often sit on their haunches for 30 seconds to several minutes at a time
- forelimbs held loosely
- tail is used for support

abnormal reflex
- increased sensitivity to intentional sound stimuli not related to hearing

abnormal sexual interaction
- do not breed although health is good and ovaries are reported to be functional

convulsive seizures
- all show class IV seizures and 7/9 show class V seizures

increased startle reflex
- hyperstartle response

seizures
- by 3 weeks of age, motor disturbances such as partial seizures, jittering, fluctuating hemiplegia were seen
- overall symptoms suggestive of epilepsy

tonic-clonic seizures
- running seizures, rearing and falling, postanaesthetic tonic-clonic seizures were reported

tremors
- body tremors
- jittering

growth/size/body region phenotype

decreased body size
- smaller in size than controls

hearing/vestibular/ear phenotype

abnormal hearing physiology
- abnormal audiosensitivity

ear inflammation
- crusting in the outer ear

immune system phenotype

ear inflammation
- crusting in the outer ear

eye inflammation
- crusting of the eyelid

nervous system phenotype

abnormal astrocyte morphology
- brains at 4 months of age show a slight increase in the number of astrocytes in the hippocampus

abnormal brain development
- growth continued well past 2 weeks when it normally stops
- growth involved cell hypertrophy rather than hyperplasia
- lipid as a percentage of the brain composition was decreased

abnormal brain morphology

abnormal brain size

convulsive seizures
- all show class IV seizures and 7/9 show class V seizures

enlarged hippocampus
- by 66%

increased brain size
- brains were grossly larger than littermates
- by 4-6 months of age there was some protrusion of the cerebellar vermis through the foramen magnum
- coronal area of the brain, total volume, hippocampal formation, and cerebral cortex were also enlarged at 8 weeks of age and later
- greatest increase in size was in the ventral cortex
- thalamus, cerebellum, spinal cord were all relatively normal in size

increased brain weight
- brains were significantly heavier than normal from 2 months on

seizures
- by 3 weeks of age, motor disturbances such as partial seizures, jittering, fluctuating hemiplegia were seen
- overall symptoms suggestive of epilepsy

tonic-clonic seizures
- running seizures, rearing and falling, postanaesthetic tonic-clonic seizures were reported

vision/eye phenotype

chromodacryorrhea
- eye discharge creates a channel of red discoloration due to the red-staining porphyrin contained in mouse tears

excessive tearing
- tearing from medial canthus of eyes which becomes continuous and is often associated with inflammation and crusting

eye inflammation
- crusting of the eyelid

References

Additional References

Petersson S; Sandberg Nordqvist A; Schalling M; Lavebratt C. 1999. The megencephaly mouse has disturbances in the insulin-like growth factor (IGF) system. Brain Res Mol Brain Res 72(1):80-8PubMed: 10521601 MGI: J:57895

Additional - Kcna1^mceph related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the megencephaly mouse strain in a publication, please cite the originating article(s) and include JAX stock #002434 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
	Heterozygous or Wild-type for Kcna1<mceph>

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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

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Also Known As:megencephaly

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Kcna1mceph

Allele Symbol: Kcna1mceph

Disease Terms

Research Areas By Phenotype

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

Genotype: Kcna1mceph related

Mammalian Phenotype Terms by Genotype

Genotype: Kcna1mceph/Kcna1mcephBALB/cByJ-Kcna1/J

behavior/neurological phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

immune system phenotype

nervous system phenotype

vision/eye phenotype

References

Additional References

Additional - Kcna1mceph related

Genotyping Protocols

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

Kcna1^mceph

Allele Symbol: Kcna1^mceph

Genotype: Kcna1^mceph related

Genotype: Kcna1^mceph/Kcna1^mceph
BALB/cByJ-Kcna1/J

Additional - Kcna1^mceph related