Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N10F?+2pN1 Generation Definitions   Donating Investigator Mark D Fleming,   Children's Hospital Boston

Description
Homozygous mice are viable and fertile with no reported neurological or hematological abnormalities. These mutant mice have loxP sites flanking exons 9 and 10 of the endogenous gene. When bred to Cre recombinase expressing mice, exons 9 and 10 are deleted in the offspring dependent on the tissue specificity of the Cre recombinase expressing parent. The donating investigator reports that the null allele is not transmissible due to an effect on the extraembryonic tissues. This mutant may be useful in studying cytosolic Fe-S cluster assembly and metabolism, Friedreich ataxia, anemia, and hematopoiesis.

When bred to a strain expressing Cre recombinase in liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of hepatocyte iron metabolism.

When bred to a strain expressing Cre recombinase in epiblast derived cells (see Stock No. 004783, 008454 for example), this mutant mouse strain may be useful in development studies.

Development
A targeting vector was designed to insert a loxP site into intron 8 and a loxP-flanked neomycin resistance cassette into intron 10 of the X-linked endogenous gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. Correctly targeted ES cells (with loxP sites flanking exons 9 and 10) were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6J to establish the colony. Mutant mice were backcrossed to C57BL/6J mice for 10 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Anemia, Sideroblastic, and Spinocerebellar Ataxia; ASAT   (ABCB7)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Abcb7^tm1Mdf/Abcb7⁺ Tg(Sox2-cre)1Amc/0

        either: B6.Cg-Abcb7^tm1Mdf Tg(Sox2-cre)1Amc or (involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * CBA)   (conditional)

• mortality/aging
• *normal* mortality/aging
  • females are viable   (MGI Ref ID J:106838)

Abcb7^tm1Mdf/Y Tg(Alb-cre)21Mgn/0

        either: B6.Cg-Abcb7^tm1Mdf Tg(Alb-cre)21Mgn or (involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * DBA)   (conditional)

• liver/biliary system phenotype
• abnormal liver morphology
  • mild hepatic architectural disarray and hepatocellular multinucleation are seen   (MGI Ref ID J:106838)
• • abnormal hepatocyte morphology
    • many cytosolic lipid droplets and pale swollen mitochondria are seen suggesting metabolic or mitochondrial damage   (MGI Ref ID J:106838)
    • multinucleated hepatocytes are seen   (MGI Ref ID J:106838)
• homeostasis/metabolism phenotype
• abnormal circulating enzyme level
  • 2-fold increase in serum levels of liver-derived transaminases indicative of liver damage   (MGI Ref ID J:106838)
• abnormal enzyme/coenzyme activity
  • 50% reduction in hepatic activity of xanthine oxidase; however no change in expression is detected   (MGI Ref ID J:106838)
  • about a 20% decrease in hepatic mitochondrial activity of succinate dehydrogenase when normalized to cytochrome C oxidase activity   (MGI Ref ID J:106838)
  • about a 90% and 60% decrease in cytosolic aconitate hydratase 1 (Aco1) activity and protein, respectivly, are seen in the liver   (MGI Ref ID J:106838)
• hemosiderosis
  • 76% increase in total liver iron; however, serum iron and total iron binding capacity are similar to controls and no signs of mitochondrial iron overload are detected   (MGI Ref ID J:106838)
  • a small subset of hepatocytes particularly cells adjacent to a portal triad or central vein, contain abundant, coarsely granular cytosolic iron deposits   (MGI Ref ID J:106838)

Abcb7^tm1Mdf/Y Tg(Sox2-cre)1Amc/0

        either: B6.Cg-Abcb7^tm1Mdf Tg(Sox2-cre)1Amc or (involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * CBA)   (conditional)

• mortality/aging
• complete embryonic lethality between somite formation and embryo turning
  • die at E7.5 - E8.5   (MGI Ref ID J:106838)

View Research Applications

Research Applications

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

Hematological Research
Anemia, Iron Deficiency and Transport Defects
Anemia, Iron Homeostasis Defects

Neurobiology Research
Ataxia (Movement) Defects
Friedreich's Ataxia

Research Tools
Cardiovascular Research
      Cre-lox System
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Hematological Research
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Abcb7tm1Mdf
Allele Name		targeted mutation 1, Mark D Fleming
Allele Type		Targeted (Floxed/Frt)
Mutation Made By		Mark Fleming,   Children's Hospital Boston
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Abcb7, ATP-binding cassette, sub-family B (MDR/TAP), member 7
Chromosome		X
Gene Common Name(s)		AA517758; ABC7; ASAT; ATP-binding cassette 7; AU019072; Abc7; Atm1p; EST140535; expressed sequence AA517758; expressed sequence AU019072;
Molecular Note		LoxP sites were inserted into the locus to flank exons 9 and 10. Transient cre expression removed a neomycin resistance cassette included in the vector. [MGI Ref ID J:106838]

Genotyping

Genotyping Information

Genotyping Protocols

Abcb7^tm1Mdf, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Clarke SL; Vasanthakumar A; Anderson SA; Pondarre C; Koh CM; Deck KM; Pitula JS; Epstein CJ; Fleming MD; Eisenstein RS. 2006. Iron-responsive degradation of iron-regulatory protein 1 does not require the Fe-S cluster. EMBO J 25(3):544-53. [PubMed: 16424901]  [MGI Ref ID J:105934]

Additional References

Abcb7^tm1Mdf related

Pondarre C; Antiochos BB; Campagna DR; Clarke SL; Greer EL; Deck KM; McDonald A; Han AP; Medlock A; Kutok JL; Anderson SA; Eisenstein RS; Fleming MD. 2006. The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis. Hum Mol Genet 15(6):953-64. [PubMed: 16467350]  [MGI Ref ID J:106838]

Pondarre C; Campagna DR; Antiochos B; Sikorski L; Mulhern H; Fleming MD. 2007. Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. Blood 109(8):3567-9. [PubMed: 17192398]  [MGI Ref ID J:136594]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	The targeted gene is on the X chromosome. When maintaining a live colony, homozygous females are bred to hemizygous males.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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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.

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Terms of Use

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General Terms and Conditions

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