Overview

This Abca2 knockout strain may be useful in studies of myelin sheath development, oligodendrocyte differentiation, tremor without ataxia, and hyperactivity.

Donating Investigator

Kenneth D. Tew, Medical University of South Carolina

Genetic overview

Genetic Background	Generation

Abca2^tm1Kdt

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Abca2	ATP-binding cassette, sub-family A (ABC1), member 2

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Although homozygotes are viable and fertile, few pups born to homozygous females survive. The Donating Investigator maintains the C57BL/6 congenic strain using heterozygous crosses. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis of cerebrum, cerebellum, spinal cord, heart, lung, kidney, liver, spleen, thymus, uterus, prostate, and ovary. Homozygotes exhibit a quivering or shaking phenotype and are more easily startled by sound, hence the "skittish" nickname designation. The tremor is without ataxia. Homozygotes exhibit hyperactivity. Although growth rate and food consumption are similar to wildtype controls, homozygotes have a reduced body weight. The observed hyperactivity and reduced body weight is more significant in female homozygotes. Ultrastructural analysis of myelin sheath in cerebrum and spinal cord reveals increased myelin sheath thickness in the spinal cord and defective myelin compaction (membrane periodicity) in both spinal cord and cerebrum. An increased number of mitochondria is observed by ultrastructural analysis of sciatic nerve.

When crossed with TRAMP transgenic mice (Stock No. 003135) the double mutant mice, 20-25 weeks in age, exhibit no detectable metastases, while 38% of wild-type littermates carrying the TRAMP transgene alone developed metastases in the lung and/or lymph nodes.

Development

A targeting vector containing a Neo selection cassette was used to disrupt exons 23 through 30, which encodes the first nucleotide-binding domain of the transporter. The construct was electroporated into 129/Sv derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The mice were backcrossed to C57BL/6J for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Mack JT; Beljanski V; Soulika AM; Townsend DM; Brown CB; Davis W; Tew KD. 2007. 'Skittish' Abca2 knockout mice display tremor, hyperactivity, and abnormal myelin ultrastructure in the central nervous system. Mol Cell Biol 27(1):44-53PubMed: 17060448 MGI: J:117673

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Genetics

Abca2^tm1Kdt

Allele Symbol: Abca2^tm1Kdt

Allele Name	targeted mutation 1, Kenneth D Tew
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Abca2^-
Gene Symbol and Name	Abca2, ATP-binding cassette, sub-family A (ABC1), member 2
Gene Synonym(s)
Strain of Origin	129/Sv
Chromosome	2
Molecular Note	Exons 23-30 were replaced with a neomycin resistance cassette. This sequence encoded the first nucleotide binding domain.
Mutations Made By	Kenneth Tew, Medical University of South Carolina

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Tremor Defects
- Myelination Defects
- Behavioral and Learning 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: Abca2^tm1Kdt/Abca2^tm1Kdt
involves: 129

behavior/neurological phenotype

abnormal motor coordination/balance
- impaired ability to counterbalance body weight on 4 paws when placed perpendicular to beam
- mutants move more rapidly on beam, with tendency to fall, compared to wild-type

enhanced coordination
- mutants perform better on rotarod apparatus at 4, 8, and 15 weeks of age

hyperactivity
- increased movement in cages is seen in males at 30- and 55-minute time points and in females from 10 to 60 minutes, along with increased climbing behavior

increased fear-related response
- mice are more frightened by handlers, and are more difficult to catch by the tail compared to wild-type littermates

increased startle reflex
- mice are more easily startled by sound

increased vertical activity
- increased rearing and increased climbing behavior compared to controls is observed

tremors
- during ambulation, shaking motion of ears, tail and body are observed in contrast to control littermates
- tremors in fore and hindlimbs is observed on balance beam or upon suspension by tail; abrupt undulating movements along spine are seen when mice are suspended

growth/size/body region phenotype

decreased body weight
- lower body weight in males at 5-6 weeks of age, and in females from 4-14 weeks compared to controls

nervous system phenotype

abnormal myelin sheath morphology
- (5% and 0%); mutant axons show hypomyelination
- average myelin sheath thickness in spinal cord of female mutants (0.2 um) is increased vs wild-type (.12 um)
- elinated
- in cerebrum and spinal cord of mutants, reduced periodicity and compaction of myelin is displayed
- in cerebrum, more axons in mutants (24.1%) are in smallest range of myelin thickness than in wild-type (12.8%); more wild-type cerebral axons are in higher size ranges (8.5% with .16-.2 um thickness; 7.5% with >.21 um myelin thickness) compared to mutants (5% and 0%); mutant axons show hypomyelination
- in spinal cord, less axons (23.2%) in mutants have lower sheath measurements than in wild-type (34.4%); mutant axons predominate in higher (13.6% at .65-.94 um; 10.6% at >.94%) compared to wild-type (4.5% and 1.4%, respectively); mutant axons are hypermyelinated

References

Mack JT; Beljanski V; Soulika AM; Townsend DM; Brown CB; Davis W; Tew KD. 2007. 'Skittish' Abca2 knockout mice display tremor, hyperactivity, and abnormal myelin ultrastructure in the central nervous system. Mol Cell Biol 27(1):44-53PubMed: 17060448 MGI: J:117673

Additional - Abca2^tm1Kdt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Abca2 alternative 1
- Separated MCA:Abca2 alternative 1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes, however few pups born to homozygous females survive. The Donating Investigator maintains the C57BL/6 congenic strain using heterozygous crosses.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129-Abca2^tm1Kdt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012465 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 Wildtype for Abca2<tm1Kdt>

Related Products and Services

Frozen Mouse Embryo	B6.129-Abca2<tm1Kdt>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Abca2<tm1Kdt>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Abca2<tm1Kdt>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129-Abca2<tm1Kdt>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Abca2tm1Kdt

Allele Symbol: Abca2tm1Kdt

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Abca2tm1Kdt/Abca2tm1Kdtinvolves: 129

behavior/neurological phenotype

growth/size/body region phenotype

nervous system phenotype

References

Additional - Abca2tm1Kdt 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

Related Products and Services

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

Abca2^tm1Kdt

Allele Symbol: Abca2^tm1Kdt

Genotype: Abca2^tm1Kdt/Abca2^tm1Kdt
involves: 129

Additional - Abca2^tm1Kdt related