Overview

The Acc2^flox allele has loxP sites flanking the biotin-binding motif exon (and the preceding exon) of the acetyl-Coenzyme A carboxylase beta (Acacb or Acc2) locus. The exon immediately upstream of the biotin-binding catalytic domain was included so that splicing of the remaining exons following Cre-mediated deletion would introduce a frameshift and nonsense mutation after Asp865 in any translated protein. These mutant mice may be useful to generate conditional mutations for studying malonyl-CoA (the substrate for fatty acid synthesis and the regulator of fatty acid oxidation) synthesis and other metabolic cellular signaling molecules, as well as diet-induced obesity, glucose intolerance and insulin resistance.

Donating Investigator

Bradford B. Lowell, Beth Israel Deaconess Med Cntr (Harvard)

Genetic overview

Genetic Background	Generation

Acacb^tm1.1Lowl

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Acacb	acetyl-Coenzyme A carboxylase beta

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Research Applications

Metabolism Research
Research Tools
Cardiovascular 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 Acc2^flox allele are viable, fertile, normal in size, and have no reported physical abnormalities. The Acc2^flox allele has loxP sites flanking the biotin-binding motif exon (and the preceding exon) of the targeted locus. When bred to mice that express Cre recombinase, the resulting offspring will have the floxed sequences deleted in the cre-expressing cells/tissues. The exon immediately upstream of the biotin-binding catalytic domain was included so that splicing of the remaining exons following Cre-mediated deletion would introduce a frameshift and nonsense mutation after Asp865 in any translated protein. These mutant mice may be useful to generate conditional mutations for studying malonyl-CoA (the substrate for fatty acid synthesis and the regulator of fatty acid oxidation) synthesis and other metabolic cellular signaling molecules, as well as diet-induced obesity, glucose intolerance and insulin resistance.

NOTE: When these Acc2^flox mice are bred with germline cre-expressing mice (B6.FVB-Tg(Zp3-cre)3Mrt/J (Stock No. 003394)), the resulting offspring may be bred together to generate Acc2-deficient (Acc2KO) homozygous mice. Such pan Acc2KO homozygotes exhibit reduced total acetyl CoA carboxylase (ACC) activity in skeletal muscle, reduced heart size, decreased cardiac malonyl CoA levels, and a slight increase in energy expenditure (increased oxygen consumption during the dark cycle). Except for the increase in energy expenditure, this pan Acc2KO phenotype is similar to that reported for Acc2-deficient mice lacking exon 12 (Acacb^tm1Dejs; Hoehn et al., 2010 Cell Metab 11:70). However, the pan Acc2KO mice are not reported to display any of the abnormal metabolic effects described for Acacb^tm1Sjw homozygous mice (including reduced fat storage, continuous fatty acid oxidation, improved insulin sensitivity, and protection against obesity and diabetes induced by high-fat/high-carbohydrate diets) (Abu-Elheiga et al., 2001 Science 291:2613). Like the Acc2KO allele, the Acacb^tm1Sjw allele also lacks the biotin-binding domain. Unlike the Acc2KO allele, the Acacb^tm1Sjw allele retains the upstream exon (leaving the mutant RNA in-frame).

Development

A targeting vector was designed to insert a frt-flanked kanamycin cassette and a loxP site downstream of the biotin-binding domain exon, as well as a loxP site upstream of the preceding exon of the Acetyl-CoA carboxylase 2 (Acacb or Acc2) locus. The exon immediately upstream of the catalytic domain was included so that splicing of the remaining exons following Cre-mediated deletion would introduce a frameshift and nonsense mutation after Asp865 in any translated protein. The construct was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6NCrl mice to establish the colony. The mutant mice were then bred to mice expressing Flp recombinase (R26-FLPe on a 129S4 genetic background; see Stock No. 003946) to remove the frt-flanked neo cassette. The resulting Acc2^flox mice had a loxP site upstream of the preceding exon, and a single frt site and second loxP site downstream of the biotin binding domain exon. Acc2^flox mice were maintained on this C57BL/6N;129 mixed genetic background (and the R26-FLPe allele was removed) prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Olson DP; Pulinilkunnil T; Cline GW; Shulman GI; Lowell BB. 2010. Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake. Proc Natl Acad Sci U S A 107(16):7598-603PubMed: 20368432 MGI: J:159285

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Genetics

Acacb^tm1.1Lowl

Allele Symbol: Acacb^tm1.1Lowl

Allele Name	targeted mutation 1.1, Bradford B Lowell
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Acc2^flox
Gene Symbol and Name	Acacb, acetyl-Coenzyme A carboxylase beta
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	5
Molecular Note	LoxP sites were positioned upstream of the preceding exon and downstream of the biotin binding domain exon, with an Frt flanked kanamycin resistance cassette inserted before the 3' loxP site. The Frt-flanked selection cassette was removed by Flpe recombinase-mediated recombination. Splicing of the remaining exons following Cre-mediated deletion would introduce a frameshift and nonsense mutation after Asp865 in any translated protein.
Mutations Made By	Bradford Lowell, Beth Israel Deaconess Med Cntr (Harvard)

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Metabolism Research
- Lipid Metabolism
Research Tools
- Metabolism Research
- Genetics Research
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: Cre-lox System
- Diabetes and Obesity Research
  - loxP
- Cardiovascular Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
Cardiovascular Research
- Other
  - altered fat metabolism
- Metabolic Syndrome

Mammalian Phenotype Terms by Genotype

References

Olson DP; Pulinilkunnil T; Cline GW; Shulman GI; Lowell BB. 2010. Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake. Proc Natl Acad Sci U S A 107(16):7598-603PubMed: 20368432 MGI: J:159285

Additional - Acacb^tm1.1Lowl related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Acacb
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the B6N;129S-Acacb^tm1.1Lowl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013042 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 Acacb<tm1.1Lowl>

Related Products and Services

Frozen Mouse Embryo	B6N;129S-Acacb<tm1.1Lowl>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N;129S-Acacb<tm1.1Lowl>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N;129S-Acacb<tm1.1Lowl>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6N;129S-Acacb<tm1.1Lowl>/J Frozen Embryo	$3373.50

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Acacbtm1.1Lowl

Allele Symbol: Acacbtm1.1Lowl

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Acacbtm1.1Lowl 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

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Acacb^tm1.1Lowl

Allele Symbol: Acacb^tm1.1Lowl

Additional - Acacb^tm1.1Lowl related