Description

Strain Information

Type Coisogenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   08-JAN-10 Species laboratory mouse Generation N15+N1F78 (15-AUG-11) Generation Definitions   Donating Investigator James Wang,   Harvard University

Description
These mice possess loxP sites flanking the 3 exons encoding the active-site tyrosyl residue 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 the 3 exons deleted in the cre-expressing tissue(s).

When bred to a strain expressing Cre recombinase during spermatogenesis (see Stock No. 003328 for example), this mutant mouse strain may be useful in studies of neural development.

When bred to a strain expressing Cre recombinase in the telencephalon and discreet head structures (see Stock No. 004337, 006084 for example), this mutant mouse strain may be useful in studies of corticogenesis.

Development
A targeting vector was designed to insert a loxP site and self-excising selection cassette upstream, and a second loxP site downstream of the three exons that encode the active-site tyrosyl residue of the targeted gene. The self-excising selection cassette, containing PGK-neo and FLPe recombinase gene under the control of angiotensin-converting enzyme promoter, is flanked by frt sites. FLPe-mediated recombination during spermatogenesis removed the cassette, leaving one loxP and frt site upstream, and the second loxP site downstream of the three targeted exons. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred to 129SvEv (Taconic) females to generate top2β^flox2 mice. These mice were then backcrossed to 129SvEv (Taconic) for approximately 15 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were backcrossed to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

Control Information

	Control
	002448 129S1/SvImJ
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Top2b^tm2Jcw/Top2b^tm2Jcw

        129S6/SvEvTac

• normal phenotype
• no abnormal phenotype detected   (MGI Ref ID J:94879)

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

Foxg1^tm1(cre)Skm/Foxg1⁺ Top2b^tm2Jcw/Top2b^tm2.1Jcw

        involves: 129S4/SvJae * 129S6/SvEvTac * 129X1/SvJ   (conditional)

• mortality/aging
• complete neonatal lethality
  • died of respiratory failure within 30 min after birth, however decreased body size was not observed as in homozygous Top2b mutant mice   (MGI Ref ID J:94879)
• behavior/neurological phenotype
• abnormal motor capabilities/coordination/movement
  • lack the vigor of wild-type newborns, however show some body movements upon tactile stimulation   (MGI Ref ID J:94879)
• respiratory system phenotype
• atelectasis   (MGI Ref ID J:94879)
• respiratory failure
  • collapsed lung alveoli in dead pups suggests respiratory failure   (MGI Ref ID J:94879)
• nervous system phenotype
• abnormal cerebral cortex morphology
  • thinner cortex   (MGI Ref ID J:94879)
• abnormal hippocampus morphology   (MGI Ref ID J:94879)
• • abnormal hippocampus granule cell layer
    • ill-defined granule cell layer in the hippocampus   (MGI Ref ID J:94879)
  • abnormal hippocampus pyramidal cell layer
    • ill-defined pyramidal cell layer in the hippocampus   (MGI Ref ID J:94879)
• small olfactory bulb
  • less developed olfactory bulb   (MGI Ref ID J:94879)

View Research Applications

Research Applications

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

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Top2btm2Jcw
Allele Name		targeted mutation 2, James C Wang
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		top2betaflox1; top2betaflox2;
Mutation Made By		Lisa Lyu,   UMDNJ-Robert Wood Johnson Medical School
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC1/TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Top2b, topoisomerase (DNA) II beta
Chromosome		14
Gene Common Name(s)		D230016L12Rik; RIKEN cDNA D230016L12 gene; TOPIIB; Top-2; top2beta; topoisomerase (DNA) II;
Molecular Note		A self excising neomycine resistance cassette together with an upstream loxP site was inserted in one intron (4?) and a second loxp site was inserted in the third downstream exon. The presence or absence of the neomycin cassette was assessed by PCR but did not affect selection of mice for breeding since the resistance cassette was contained between the two loxP sites. [MGI Ref ID J:94879]

Genotyping

Genotyping Information

Genotyping Protocols

Top2b^tm2Jcw, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lyu YL; Wang JC. 2003. Aberrant lamination in the cerebral cortex of mouse embryos lacking DNA topoisomerase IIbeta. Proc Natl Acad Sci U S A 100(12):7123-8. [PubMed: 12773624]  [MGI Ref ID J:94879]

Additional References

Top2b^tm2Jcw related

Azarova AM; Lyu YL; Lin CP; Tsai YC; Lau JY; Wang JC; Liu LF. 2007. From the Cover: Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A 104(26):11014-9. [PubMed: 17578914]  [MGI Ref ID J:125761]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   08-JAN-10
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	002448 129S1/SvImJ
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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