JAX Mouse Strain Datasheet - 014162

B6.Cg-Fxn^tm1Mkn Fxn^tm1Pand/J

Stock No:: 014162 |; KIKO

Cryo Recovery

Overview

Also Known As: KIKO

Frataxin levels and pancreatic iron levels are reduced in these knock-in/knockout mice. However, unlike Friedreich's Ataxia patients, no detectable change in GAA repeat size is observed. This mutant mouse may be useful in studies of Friedreich's Ataxia.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Fxn^tm1Mkn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Fxn	frataxin

Fxn^tm1Pand

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence, Inserted expressed sequence)	Fxn	frataxin

View Genetics

Research Applications

Neurobiology Research

View All Research Applications

Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

These frataxin knock-in/knockout (KIKO) mice harbor one allele of the frataxin (GAA)₂₃₀ expansion mutation (Fxn^tm1Pand) on one chromosome, and one allele of the frataxin exon 4-deleted mutation (Fxn^tm1Mkn) on the homologous chromosome. KIKO mice are viable and fertile. Analysis of frataxin levels in tissues from KIKO mice demonstrate a reduction of frataxin to 25-36% of wildtype controls. KIKO animals up to 1 year of age perform equivalent to wildtype controls on rotarod test. Total iron concentrations were similar in all tested tissues of KIKO and wildtype mice except in pancreas: KIKO mice demonstrate lower iron levels in pancreatic tissues. No iron deposits and only mild collagen staining around the vessels of the heart were observed in both year old KIKO mice and wildtype controls. In contrast to Friedreich's Ataxia patients, no detectable change in GAA repeat size was found over six studied generations. Moreover, no evidence of somatic cell instability was noted as GAA repeat expansion size was the same in all analyzed tissues. However, characterization of KIKO mice performed at The Jackson Laboratory revealed that starting at 6 months of age, these animals exhibit an abnormal "weaving" gait when subjected to a forced treadmill walk. This phenotype occurs with increasing penetrance as the mice age. This mutant mouse may be useful in studies of Friedreich's Ataxia.

Importation of this model was supported by the Friedreich's Ataxia Research Alliance (FARA).

Development

To generate these frataxin knock-in/knockout animals (KIKO), mice heterozygous for the frataxin (GAA)₂₃₀ expansion mutation (Fxn^tm1Pand) were bred with mice heterozygous for the frataxin exon 4-deleted mutation (Fxn^tm1Mkn). Progeny bearing both the GAA expansion (knock-in) allele and the exon 4-deleted (knockout) allele were bred together, and given the Stock No. 014162. These KIKO mice no longer harbor the Tg(FXN)YG8Pook transgene.

For a description of the frataxin (GAA)₂₃₀ expansion mutation (Fxn^tm1Pand), please see Stock No. 008470.

For a description of the frataxin exon 4-deleted mutation (Fxn^tm1Mkn), please see the compound mutant Stock No. 012253.

Expression Data

Expressed Gene	Fxn, frataxin, mouse, laboratory
Site of Expression
Site of Expression

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Cossee M; Puccio H; Gansmuller A; Koutnikova H; Dierich A; LeMeur M; Fischbeck K; Dolle P; Koenig M. 2000. Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum Mol Genet 9(8):1219-26. PubMed: 10767347 MGI: J:62185
Miranda CJ; Santos MM; Ohshima K; Smith J; Li L; Bunting M; Cossee M; Koenig M; Sequeiros J; Kaplan J; Pandolfo M. 2002. Frataxin knockin mouse. FEBS Lett 512(1-3):291-7. PubMed: 11852098 MGI: J:109164

View All References

Genetics

Fxn^tm1Mkn

Allele Symbol: Fxn^tm1Mkn

Allele Name	targeted mutation 1, Michel Koenig
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Frda^-; Frda^del4
Gene Symbol and Name	Fxn, frataxin
Gene Synonym(s)	CyaY; FA; FARR; FRDA; Frda; Frda; Friedreich ataxia; RGD1565754; X25
Expressed Gene	Fxn, frataxin, mouse, laboratory
Strain of Origin	129/Sv
Chromosome	19
Molecular Note	A loxP-flanked PGK-neomycin resistance cassette replaced a genomic DNA fragment containing exon 4, which is highly conserved and often mutated in humans. An additional line was also produced in which the loxP flanked neomycin cassette was removed by Cre mediated recombination, but no distinction was made between these alleles in the original reference. From J:90098: The presence of a human FRDA transgene in hemizygous form in a Frda^tm1Mkn homozygous null background rescues the embryonic lethal phenotype and complements for the loss of endogenous mouse frataxin.

Fxn^tm1Pand

Allele Symbol: Fxn^tm1Pand

Allele Name	targeted mutation 1, Massimo Pandolfo
Allele Type	Targeted (Humanized sequence, Inserted expressed sequence)
Allele Synonym(s)	frda^230GAA
Gene Symbol and Name	Fxn, frataxin
Gene Synonym(s)	CyaY; FA; FARR; FRDA; Frda; Frda; Friedreich ataxia; RGD1565754; X25
Promoter	Fxn, frataxin, mouse, laboratory
Strain of Origin	129/Sv
Chromosome	19
Molecular Note	A targeting vector was designed to insert a GAA230 repeat expansion and a floxed neomycin resistance cassette into intron 1 of the locus. Western blot demonstrated that mutants expressed frataxin protein at 75% of wild-type levels in all tissues examined.
Mutations Made By	Massimo Pandolfo, Universite Libre de Bruxelles

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Friedreich's Ataxia

Mammalian Phenotype Terms by Genotype

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

Genotype: Fxn^tm1Mkn/Fxn^tm1Pand
involves: 129/Sv * C57BL/6

mortality/aging

premature death
- 2/13 mice died during the course of the experiment; 1 of these died at about 12 months of age

homeostasis/metabolism phenotype

increased heart iron level
- the mouse that died at about 12 months of age had 3-fold higher iron levels in the heart than littermates (1168 ug vs 399 ug)

cardiovascular system phenotype

cardiac fibrosis
- the mouse that died at ~ 12 months showed prominent heart fibrosis

increased heart iron level
- the mouse that died at about 12 months of age had 3-fold higher iron levels in the heart than littermates (1168 ug vs 399 ug)

immune system phenotype

brain inflammation
- inflammatory arachidonic metabolites are elevated in cerebellum

nervous system phenotype

brain inflammation
- inflammatory arachidonic metabolites are elevated in cerebellum

References

Cossee M; Puccio H; Gansmuller A; Koutnikova H; Dierich A; LeMeur M; Fischbeck K; Dolle P; Koenig M. 2000. Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum Mol Genet 9(8):1219-26. PubMed: 10767347 MGI: J:62185
Miranda CJ; Santos MM; Ohshima K; Smith J; Li L; Bunting M; Cossee M; Koenig M; Sequeiros J; Kaplan J; Pandolfo M. 2002. Frataxin knockin mouse. FEBS Lett 512(1-3):291-7. PubMed: 11852098 MGI: J:109164

Additional - Fxn^tm1Mkn related

Al-Mahdawi S; Pinto RM; Ruddle P; Carroll C; Webster Z; Pook M. 2004. GAA repeat instability in Friedreich ataxia YAC transgenic mice. Genomics 84(2):301-10. PubMed: 15233994 MGI: J:91581
Al-Mahdawi S; Pinto RM; Varshney D; Lawrence L; Lowrie MB; Hughes S; Webster Z; Blake J; Cooper JM; King R; Pook MA. 2006. GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology. Genomics 88(5):580-90. PubMed: 16919418 MGI: J:114840
Anjomani Virmouni S; Ezzatizadeh V; Sandi C; Sandi M; Al-Mahdawi S; Chutake Y; Pook MA. 2015. A novel GAA repeat expansion-based mouse model of Friedreich ataxia. Dis Model Mech :. PubMed: 25681319 MGI: J:217862
Anjomani Virmouni S; Sandi C; Al-Mahdawi S; Pook MA. 2014. Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia. PLoS One 9(9):e107416. PubMed: 25198290 MGI: J:217861
Cloonan SM; Glass K; Laucho-Contreras ME; Bhashyam AR; Cervo M; Pabon MA; Konrad C; Polverino F; Siempos II; Perez E; Mizumura K; Ghosh MC; Parameswaran H; Williams NC; Rooney KT; Chen ZH; Goldklang MP; Yuan GC; Moore SC; Demeo DL; Rouault TA; D'Armiento JM; Schon EA; Manfredi G; Quackenbush J; Mahmood A; Silverman EK; Owen CA; Choi AM. 2016. Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice. Nat Med 22(2):163-74. PubMed: 26752519 MGI: J:233150
Hayashi G; Shen Y; Pedersen TL; Newman JW; Pook M; Cortopassi G. 2014. Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich's ataxia. Hum Mol Genet 23(25):6838-47. PubMed: 25104852 MGI: J:216422
Jasoliya MJ; McMackin MZ; Henderson CK; Perlman SL; Cortopassi GA. 2017. Frataxin deficiency impairs mitochondrial biogenesis in cells, mice and humans. Hum Mol Genet 26(14):2627-2633. PubMed: 28444186 MGI: J:242978
Jones J; Estirado A; Redondo C; Martinez S. 2013. Stem cells from wildtype and friedreich's ataxia mice present similar neuroprotective properties in dorsal root ganglia cells. PLoS One 8(5):e62807. PubMed: 23671637 MGI: J:202178
Molla B; Riveiro F; Bolinches-Amoros A; Munoz-Lasso DC; Palau F; Gonzalez-Cabo P. 2016. Two different pathogenic mechanisms, dying-back axonal neuropathy and pancreatic senescence, are present in the YG8R mouse model of Friedreich ataxia. Dis Model Mech :. PubMed: 27079523 MGI: J:232478
Pook MA; Al-Mahdawi S; Carroll CJ; Cossee M; Puccio H; Lawrence L; Clark P; Lowrie MB; Bradley JL; Cooper JM; Koenig M; Chamberlain S. 2001. Rescue of the Friedreich's ataxia knockout mouse by human YAC transgenesis. Neurogenetics 3(4):185-93. PubMed: 11714098 MGI: J:213628
Sahdeo S; Scott BD; McMackin MZ; Jasoliya M; Brown B; Wulff H; Perlman SL; Pook MA; Cortopassi GA. 2014. Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia. Hum Mol Genet 23(25):6848-62. PubMed: 25113747 MGI: J:216419
Sandi C; Pinto RM; Al-Mahdawi S; Ezzatizadeh V; Barnes G; Jones S; Rusche JR; Gottesfeld JM; Pook MA. 2011. Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model. Neurobiol Dis 42(3):496-505. PubMed: 21397024 MGI: J:172875
Santos MM; Miranda CJ; Levy JE; Montross LK; Cossee M; Sequeiros J; Andrews N; Koenig M; Pandolfo M. 2003. Iron metabolism in mice with partial frataxin deficiency. Cerebellum 2(2):146-53. PubMed: 12880182 MGI: J:112348
Sarsero JP; Holloway TP; Li L; Finkelstein DI; Ioannou PA. 2014. Rescue of the Friedreich ataxia knockout mutation in transgenic mice containing an FXN-EGFP genomic reporter. PLoS One 9(3):e93307. PubMed: 24667739 MGI: J:214147
Sarsero JP; Li L; Holloway TP; Voullaire L; Gazeas S; Fowler KJ; Kirby DM; Thorburn DR; Galle A; Cheema S; Koenig M; Williamson R; Ioannou PA. 2004. Human BAC-mediated rescue of the Friedreich ataxia knockout mutation in transgenic mice. Mamm Genome 15(5):370-82. PubMed: 15170226 MGI: J:90098
Tomassini B; Arcuri G; Fortuni S; Sandi C; Ezzatizadeh V; Casali C; Condo I; Malisan F; Al-Mahdawi S; Pook M; Testi R. 2012. Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model. Hum Mol Genet 21(13):2855-61. PubMed: 22447512 MGI: J:184617

Additional - Fxn^tm1Pand related

Hayashi G; Shen Y; Pedersen TL; Newman JW; Pook M; Cortopassi G. 2014. Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich's ataxia. Hum Mol Genet 23(25):6838-47. PubMed: 25104852 MGI: J:216422
Sahdeo S; Scott BD; McMackin MZ; Jasoliya M; Brown B; Wulff H; Perlman SL; Pook MA; Cortopassi GA. 2014. Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia. Hum Mol Genet 23(25):6848-62. PubMed: 25113747 MGI: J:216419

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Fxn<tm1Mkn>Heterozygous or wildtype for Fxn<tm1Pand>

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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Also Known As: KIKO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Fxntm1Mkn

Allele Symbol: Fxntm1Mkn

Fxntm1Pand

Allele Symbol: Fxntm1Pand

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Fxntm1Mkn/Fxntm1Pandinvolves: 129/Sv * C57BL/6

mortality/aging

homeostasis/metabolism phenotype

cardiovascular system phenotype

immune system phenotype

nervous system phenotype

References

Additional - Fxntm1Mkn related

Additional - Fxntm1Pand 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

Progeny testing is not required

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

Fxn^tm1Mkn

Allele Symbol: Fxn^tm1Mkn

Fxn^tm1Pand

Allele Symbol: Fxn^tm1Pand

Genotype: Fxn^tm1Mkn/Fxn^tm1Pand
involves: 129/Sv * C57BL/6

Additional - Fxn^tm1Mkn related

Additional - Fxn^tm1Pand related