Description

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. Mating System Heterozygote x Heterozygote         (Female x Male)   02-MAR-12 Species laboratory mouse   Donating Investigator Terry Van Dyke,   NIH

Description
Aurora kinase A is critical in centrosome separation and bipolar spindle formation, and is involved in the regulation of apoptosis. These mice possess loxP sites on either side of exon 2 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissue(s).

When bred to a strain with tamoxifen-inducible Cre recombinase expression (see Stock No. 004847 for example), this mutant mouse strain may be useful in studies of mitosis and apoptosis.

Development
A loxP and FRT site flanked targeting vector containing a NEO cassette was utilized in the construction of this mutant. This selection cassette was inserted upstream of exon 2 of the targeted gene, and another loxP site was inserted upstream of exon 3. This construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Resulting chimeric male animals were backcrossed to wildtype C57BL/6J mice. These AurA^neo mice were then crossed to X-linked CMV-Cre mice, on the mixed C57BL/6J;129S5 genetic background, which express Cre recombinase under the control of the cytomegalovirus promoter knocked into the Hprt locus (Hprt^{tm1(CMV-cre)Brd}), to remove the Neo selection cassette. Mice that retained the loxP site flanked exon 2, AurA^f, were then bred to C57BL/6J mice for 7 generations to remove the Hprt^{tm1(CMV-cre)Brd} allele. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

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. Colorectal Cancer; CRC   (AURKA)

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.

Aurka^tm1.1Tvd/Aurka^tm1.1Tvd Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺

        involves: 129 * 129P2/OlaHsd * C57BL/6J   (conditional)

• cellular phenotype
• abnormal mitosis
  • following injection of tamoxifen at E10.5 most embryonic cells appear to be in prometaphase   (MGI Ref ID J:145744)
• • increased mitotic index
    • following injection of tamoxifen at E10.5 embryos show a 4 fold increase in PH3 positive cells in the thymus and lungs compared to controls   (MGI Ref ID J:145744)
• increased apoptosis
  • following injection of tamoxifen at E10.5 about a 3 fold increase in the percentage of apoptotic cells in the thymus and lungs is seen   (MGI Ref ID J:145744)

Aurka^tm1.1Tvd/Aurka^tm1.1Tvd Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor^tm1Sor

        involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J   (conditional)

• cellular phenotype
• abnormal cell nucleus morphology
  • in MEFs at later time points after OHT treatment and serum addition cells develop large aberrant nuclei with frequent micronuclei   (MGI Ref ID J:145744)
• • abnormal chromosome number
    • in MEFS after OHT treatment and serum addition increases in the population of cells with 4N and 8N DNA content are seen   (MGI Ref ID J:145744)
• abnormal mitosis
  • live cell imaging indicates a median 8 h delay in mitotic entry in MEFS after OHT treatment and serum addition compared to controls   (MGI Ref ID J:145744)
  • in MEFS after OHT treatment and serum addition more cells are in prophase and most of these show an early prophase phenotype   (MGI Ref ID J:145744)
  • in MEFS after OHT treatment and serum addition almost no cells in metaphase, anaphase, and telophase are detected   (MGI Ref ID J:145744)
  • in MEFS after OHT treatment and serum addition cells in prometaphase have a monopolar spindle with closely adjacent chromosomes, the presence of these monopolar spindles activates the spindle checkpoint   (MGI Ref ID J:145744)
• • increased mitotic index
    • in MEFS 28 h after OHT treatment and serum addition the percent of cells positive for PH3 is increased about 3 fold compared to controls   (MGI Ref ID J:145744)
    • however, the timing of the peak in PH3 positive cells is similar to controls   (MGI Ref ID J:145744)
• decreased cell proliferation
  • growth defect in MEFs following OHT treatment and serum addition   (MGI Ref ID J:145744)

View Research Applications

Research Applications

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

Apoptosis Research

Research Tools
Apoptosis Research
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Aurkatm1.1Tvd
Allele Name		targeted mutation 1.1, Terry Van Dyke
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		AurAf;
Mutation Made By		Terry Van Dyke,   NIH
Strain of Origin		129P2/OlaHsd
Gene Symbol and Name		Aurka, aurora kinase A
Chromosome		2
Gene Common Name(s)		AIK; AIRK1; ARK-1; ARK1; AU019385; AURA; AURORA2; AW539821; Aurora-A; Ayk1; BTAK; IAK; IAK1; PPP1R47; STK15; STK6; STK7; Stk6; aurora A; expressed sequence AU019385; expressed sequence AW539821; serine/threonine kinase 6;
Molecular Note		An frt and loxP flanked neo cassette was inserted into intron 1 and a third loxP site was inserted into intron 2 via homologous recombination. Cre mediated recombination removed the neo cassette leaving exon 2 floxed. [MGI Ref ID J:145744]

Genotyping

Genotyping Information

Genotyping Protocols

Aurka^tm1.1Tvd, Melt Curve Analysis

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Cowley DO; Rivera-Perez JA; Schliekelman M; He YJ; Oliver TG; Lu L; O'Quinn R; Salmon ED; Magnuson T; Van Dyke T. 2009. Aurora-A kinase is essential for bipolar spindle formation and early development. Mol Cell Biol 29(4):1059-71. [PubMed: 19075002]  [MGI Ref ID J:145744]

Additional References

Aurka^tm1.1Tvd related

Wen Q; Goldenson B; Silver SJ; Schenone M; Dancik V; Huang Z; Wang LZ; Lewis TA; An WF; Li X; Bray MA; Thiollier C; Diebold L; Gilles L; Vokes MS; Moore CB; Bliss-Moreau M; Verplank L; Tolliday NJ; Mishra R; Vemula S; Shi J; Wei L; Kapur R; Lopez CK; Gerby B; Ballerini P; Pflumio F; Gilliland DG; Goldberg L; Birger Y; Izraeli S; Gamis AS; Smith FO; Woods WG; Taub J; Scherer CA; Bradner JE; Goh BC; Mercher T; Carpenter AE; Gould RJ; Clemons PA; Carr SA; Root DE; Schreiber SL; Stern AM; Crispino JD. 2012. Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL. Cell 150(3):575-89. [PubMed: 22863010]  [MGI Ref ID J:187884]

Yoon Y; Cowley DO; Gallant J; Jones SN; Van Dyke T; Rivera-Perez JA. 2012. Conditional Aurora A deficiency differentially affects early mouse embryo patterning. Dev Biol 371(1):77-85. [PubMed: 22939930]  [MGI Ref ID J:190555]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Heterozygote x Heterozygote         (Female x Male)   02-MAR-12

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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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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