Description

Strain Information

Former Names B6(Cg)-Stk11tm1.1Sjm/J    (Changed: 20-OCT-11 ) B6.Cg-Stk11tm1.1Sjm/J    (Changed: 28-DEC-10 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   28-DEC-11 Species laboratory mouse Generation N5+ (09-MAY-11) Generation Definitions   Donating Investigator Sean J Morrison,   UT Southwestern

Description
These Stk11 mutant mice possess loxP sites flanking exons 3-6 of the serine/threonine kinase 11 (Stk11) gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Stk11 is a member of the serine/threonine kinase family and regulates cell polarity and cell division, and controls cell energy expenditure. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-6 deleted in the cre-expressing tissues. When bred to transgenic mice expressing Cre recombinase driven by myxovirus (influenza virus) resistance 1 (Mx1) promoter/enhanced elements, STK11 expression is abolished in hematopoietic cells. This strain may be useful for studying cell growth and tumor suppression.

For example, when crossed to a strain expressing tamoxifen-inducible Cre recombinase (see Stock No. 008085) or interferon-inducible Cre recombinase (see Stock No. 003556), this mutant mouse strain may be useful in studies of metabolic and cell cycle regulation.

Development
A targeting vector was designed to insert a loxP site followed by a Frt-flanked neomycin resistance cassette (neo) upstream of exon 3, and a second loxP site downstream of exon 6 of the serine/threonine kinase 11 (Stk11) gene. The construct was electroporated into Bruce4-derived C57BL/6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts from B6(Cg)-Tyr^c-2J/J mice (Stock No. 000058) and the resulting chimeric males were bred to female B6(Cg)-Tyr^c-2J/J mice to establish a colony. These mice were then bred to mice carrying Tg(ACTFLPe)9205Dym to remove the neo cassette. Offspring were then backcrossed to C57BL/6 for at least 4 generations (See SNP note below). Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. At least 11 the 32 markers on 5 chromosomes were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Control Information

	Control
	000664 C57BL/6J	(approximate)
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. Peutz-Jeghers Syndrome; PJS   (STK11) Testicular Germ Cell Tumor; TGCT   (STK11)

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.

Stk11^tm1.1Sjm/Stk11^tm1.1Sjm Tg(Mx1-cre)1Cgn/0

        involves: C57BL/6 * CBA * SJL   (conditional)

• hematopoietic system phenotype
• abnormal bone marrow cell morphology/development
  • following pIpC treatment, multipotent progenitors transiently expand then are depleted in parallel with hematopoietic stem cells unlike in Stk11^tm1Sjm homozygotes   (MGI Ref ID J:165090)
• • decreased bone marrow cell number
    • in pIpC-treated mice   (MGI Ref ID J:165090)
• abnormal bone marrow cell physiology
  • hematopoietic stem cells (HSCs)from pIpC-treated mice exhibit increased cell proliferation compared with cells from Stk11^tm1Sjm homozygotes   (MGI Ref ID J:165090)
  • 11 days after pIpC-treatment, HSCs exhibit increased apoptosis compared with cells from Stk11^tm1Sjm homozygotes   (MGI Ref ID J:165090)
  • HSCs from pIpC-treated mice fail to exhibit long-term reconstitution unlike cells from Stk11^tm1Sjm homozygotes   (MGI Ref ID J:165090)
  • however, mice exhibit normal proliferation of granulocyte macrophage progenitors (GMP) and whole bone marrow (WBM) cells and apoptosis of multipotent progenitor, GMP, and WBM cells   (MGI Ref ID J:165090)
• decreased erythrocyte cell number
  • in pIpC-treated mice   (MGI Ref ID J:165090)
• decreased hematopoietic stem cell number
  • 18 days after pIpC treatment; not improved by rapamycin treatment   (MGI Ref ID J:165090)
• decreased leukocyte cell number
  • in pIpC-treated mice   (MGI Ref ID J:165090)
• decreased platelet cell number
  • in pIpC-treated mice   (MGI Ref ID J:165090)
• increased hematopoietic stem cell number
  • starting 2 to 6 days after pIpC treatment   (MGI Ref ID J:165090)
• pancytopenia
  • by day 24 to 34 of pIpC treatment   (MGI Ref ID J:165090)
• thymus hypoplasia
  • in pIpC-treated mice   (MGI Ref ID J:165090)
• cellular phenotype
• *normal* cellular phenotype
  • hematopoietic stem cells from pIpC treated mice exhibit normal reactive oxygen species   (MGI Ref ID J:165090)
• • abnormal mitotic spindle morphology
    • hematopoietic stem cells from pIpC-treated mice exhibit supernumerary centrosomes and defective mitotic spindle unlike in cells from similarly treated Stk11^tm1Sjm homozygotes   (MGI Ref ID J:165090)
  • aneuploidy
    • hematopoietic stem cells from pIpC-treated mice become aneuploid unlike similarly treated cells from Stk11^tm1Sjm homozygotes   (MGI Ref ID J:165090)
    • however, granulocyte macrophage progenitors cells from pIpC-treated mice do not become aneuploid   (MGI Ref ID J:165090)
  • increased mitochondrial proliferation
    • in the hematopoietic stem cells of pIpC-treated mice   (MGI Ref ID J:165090)
• immune system phenotype
• decreased leukocyte cell number
  • in pIpC-treated mice   (MGI Ref ID J:165090)
• thymus hypoplasia
  • in pIpC-treated mice   (MGI Ref ID J:165090)

Stk11^tm1.1Sjm/Stk11^tm1.1Sjm Tg(UBC-cre/ERT2)1Ejb/0

        involves: 129S/SvEv * C57BL/6 * SJL   (conditional)

• hematopoietic system phenotype
• abnormal bone marrow cell physiology
  • hematopoietic stem cells from doxycycline-treated mice fail to exhibit long-term reconstitution unlike wild-type cells   (MGI Ref ID J:165090)

View Research Applications

Research Applications

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

Cell Biology Research
Genes Regulating Growth and Proliferation

Developmental Biology Research
Growth Defects

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Stk11tm1.1Sjm
Allele Name		targeted mutation 1.1, Sean J Morrison
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Lkb1fl;
Mutation Made By		Sean Morrison,   UT Southwestern
Strain of Origin		B6.Cg-Thy1
Gene Symbol and Name		Stk11, serine/threonine kinase 11
Chromosome		10
Gene Common Name(s)		AA408040; LKB1; PJS; Par-4; R75140; expressed sequence AA408040; expressed sequence R75140; hLKB1;
Molecular Note		An FRT-flanked neo cassette with a 5'loxP site was inserted upstream of exon 3 and an additional loxP site was inserted downstream of exon 6. Flp mediated recombination removed the neo cassette. [MGI Ref ID J:165090]

Genotyping

Genotyping Information

Genotyping Protocols

Stk11^tm1Sjm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Nakada D, Saunders TL, Morrison SJ. 2010. Lkb1 regulates cell cycle and energy metabolism in hematopoietic stem cells Nature 468(7324):653-658. [PubMed: 21124450]  [MGI Ref ID J:165090]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   28-DEC-11

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J	(approximate)
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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