Overview

Also Known As: Nkx2.1-CreER

These knock-in mice express a tamoxifen-inducible cre recombinase from the endogenous promoter/enhancer elements of the NK2 homeobox 1 (Nkx2-1) gene. When induced, CreERT2 expression recapitulates endogenous Nkx2-1 expression, mainly in the medial and caudal ganglionic eminences of the basal ganglia and the preoptic area. These mice may be useful in studying the role of medial ganglionic eminences progenitor cells in GABAergic neuron development, as well as lung, thyroid, and pituitary development.

Donating Investigator

Z. Josh Huang, Cold Spring Harbor Laboratory

Genetic overview

Genetic Background	Generation
	?+N1F9 (2019-08-26 00:00:00)

Nkx2-1^{tm1.1(cre/ERT2)Zjh}

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing, Inducible)	Nkx2-1	NK2 homeobox 1

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Research Applications

Research Tools
Neurobiology Research
Cell Biology Research

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Base Price

Starting at:

$278.00 Domestic price for female 4-week

356.51 Domestic price for breeder pair

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Details

Detailed Description

The Nkx2.1-CreER (or Nkx2.1-CreERT2) knock-in allele was designed to both abolish NK2 homeobox 1 (Nkx2-1) gene function and expresseCreER^T2 fusion protein from the Nkx2-1 promoter/enhancer elements. Cre-ERT2 fusion gene activity is inducible; observed following tamoxifen administration. As such, when Nkx2.1-CreERT2 mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Nkx2-1-expressing cells of the offspring.

Heterozygous mice are viable, fertile, and normal in size with no gross physical or behavioral abnormalities reported by the donating investigator (although mice heterozygous from other null mutations of this gene exhibit impaired coordination and high thyroid-stimulating hormone levels). While the donating investigator reports the phenotype of homozygous mice as lethal, they may be expected to have defects similar to mice homozygous for other null mutations of this gene (including profound abnormalities of the ventral forebrain and lungs, a complete lack of thyroids, pituitary gland, and tracheo-esophageal septation, and perinatal death from respiratory failure).

Nkx2.1 mRNA or protein expression from the Nkx2.1-CreER mutant allele was not determined. The donating investigator reports tamoxifen-inducible Cre recombinase activity is specific and efficient; largely recapitulating the endogenous Nkx2-1 expression pattern, with highly efficient inducibility. Tamoxifen-inducible Cre recombinase activity was not tested prior to tamoxifen treatment. Following tamoxifen administration, Cre recombinase activity is observed in Nkx2.1 positive cells; including medial ganglionic eminence (MGE) progenitor cells and preoptic area. The donating investigators did not examine cre expression in tissues other than brain.

For characterization information, see images at the Allen Institute for Brain Science website (Nkx2-1-CreERT2 images).

The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.

Development

A targeting vector was designed to insert a CreER^T2 fusion gene (Cre-ER^T2; Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain), an SV40 polyA signal, and an frt-flanked neo cassette into the initiation codon of the NK2 homeobox 1 locus (Nkx2-1). This construct was electroporated into (C57BL/6 x 129S4Sv/Jae)-derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6 mice to originate the colony. Mutant mice were bred with Actin-FLPe mice (on a C57BL/6 congenic background (N10); see Stock No. 005703) to remove the neo selection cassette. These Nkx2.1-CreER (or Nkx2.1-CreERT2) mice were subsequently bred to C57BL/6 inbred mice for a few additional generations (and the FLPe transgene was removed). Next, Nkx2.1-CreERT2 mice were bred with Swiss Webster mice for several generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the Nkx2.1-CreERT2 colony.

Expression Data

Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Following tamoxifen administration, Cre recombinase activity is observed in Nkx2.1 positive cells; including medial ganglionic eminence progenitor cells and preoptic area of the brain.

Control Suggestions

Wild-type from the colony

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

NIH Neuroscience Blueprint Cre Driver Network. 2009. Cre recombinase-expressing mice generated for the NIH Neuroscience Blueprint Cre Driver Network MGI Direct Data SubmissionMGI: J:151755
Taniguchi H; He M; Wu P; Kim S; Paik R; Sugino K; Kvitsani D; Fu Y; Lu J; Lin Y; Miyoshi G; Shima Y; Fishell G; Nelson SB; Huang ZJ. 2011. A resource of cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71(6):995-1013PubMed: 21943598 MGI: J:177261
Taniguchi H; Lu J; Huang ZJ. 2013. The spatial and temporal origin of chandelier cells in mouse neocortex. Science 339(6115):70-4PubMed: 23180771 MGI: J:190658

View All References

Genetics

Nkx2-1^{tm1.1(cre/ERT2)Zjh}

Allele Symbol: Nkx2-1^{tm1.1(cre/ERT2)Zjh}

Allele Name	targeted mutation 1.1, Z Josh Huang
Allele Type	Targeted (Recombinase-expressing, Inducible)
Allele Synonym(s)	targeted mutation 1.1, Z Josh Huang; Nkx2-1^{tm1.1(cre/ERT2)Zjh}
Gene Symbol and Name	Nkx2-1, NK2 homeobox 1
Gene Synonym(s)	BHC; T/EBP; TEBP; thyroid nuclear factor 1; BCH; TTF-1; TTF1; thyroid-specific enhancer-binding protein; tinman; TITF1; AV026640; thyroid transcription factor-1; NKX2.1; NKX2A; NK-2; Ttf-1; expressed sequence AV026640; Ttf-1; Titf1; NMTC1
Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Following tamoxifen administration, Cre recombinase activity is observed in Nkx2.1 positive cells; including medial ganglionic eminence progenitor cells and preoptic area of the brain.
Strain of Origin	(C57BL/6 x 129S4/SvJae)F1
Chromosome	12
Molecular Note	A targeting vector was designed to insert a CreERT2 fusion gene , an SV40 polyA signal, and an frt-flanked neo cassette into the initiation codon of the NK2 homeobox 1 locus (Nkx2-1). This construct was electroporated into embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6 mice to originate the colony. Mutant mice were bred with Actin-FLPe mice (on a C57BL/6 congenic background) to remove the neo selection cassette. These Nkx2.1-CreER (or Nkx2.1-CreERT2) mice were subsequently bred to C57BL/6 inbred mice for a few additional generations (and the FLPe transgene was removed).
Mutations Made By	Z. Josh Huang, Cold Spring Harbor Laboratory

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis
  - Tissue/Cell Markers
  - Mutagenesis and Transgenesis: Cre-lox System
  - Tissue/Cell Markers: neurons
  - Tissue/Cell Markers: Cre-lox System
- Cre-lox System
  - Cre Recombinase Expression
  - Cre Recombinase Expression: Inducible
- Neurobiology Research
  - cell marker
Neurobiology Research
- Channel and Transporter Defects
  - chloride: GABAA receptor
- Receptor Defects
  - GABA receptor
- Cre-lox System
  - Cre Recombinase expression in neural tissue
Cell Biology Research
- Channel and Transporter Defects
  - chloride: GABAA receptor

Mammalian Phenotype Terms by Genotype

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

Genotype: Nkx2-1^{tm1.1(cre/ERT2)Zjh}/Nkx2-1⁺
involves: 129S4/SvJae * C57BL/6

mammalian phenotype

no phenotypic analysis

References

NIH Neuroscience Blueprint Cre Driver Network. 2009. Cre recombinase-expressing mice generated for the NIH Neuroscience Blueprint Cre Driver Network MGI Direct Data SubmissionMGI: J:151755
Taniguchi H; He M; Wu P; Kim S; Paik R; Sugino K; Kvitsani D; Fu Y; Lu J; Lin Y; Miyoshi G; Shima Y; Fishell G; Nelson SB; Huang ZJ. 2011. A resource of cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71(6):995-1013PubMed: 21943598 MGI: J:177261
Taniguchi H; Lu J; Huang ZJ. 2013. The spatial and temporal origin of chandelier cells in mouse neocortex. Science 339(6115):70-4PubMed: 23180771 MGI: J:190658

Additional - Nkx2-1^{tm1.1(cre/ERT2)Zjh} related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Nkx2-1^{tm1.1(cre/ERT2)Zjh}
- Probe:Gt(Rosa)26sor(CAG)
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J mice (Stock No. 000664). Homozygous mice are lethal.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the Nkx2.1-CreER mouse strain in a publication, please cite the originating article(s) and include JAX stock #014552 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Nkx2-1<tm1.1(cre/ERT2)Zjh>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Related Products and Services

Frozen Mouse Embryo	STOCK Nkx2-1<tm1.1(cre/ERT2)Zjh>/J	$2595.00
Frozen Mouse Embryo	STOCK Nkx2-1<tm1.1(cre/ERT2)Zjh>/J	$2595.00
Frozen Mouse Embryo	STOCK Nkx2-1<tm1.1(cre/ERT2)Zjh>/J	$3373.50
Frozen Mouse Embryo	STOCK Nkx2-1<tm1.1(cre/ERT2)Zjh>/J	$3373.50

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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: Nkx2.1-CreER

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Nkx2-1tm1.1(cre/ERT2)Zjh

Allele Symbol: Nkx2-1tm1.1(cre/ERT2)Zjh

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Nkx2-1tm1.1(cre/ERT2)Zjh/Nkx2-1+involves: 129S4/SvJae * C57BL/6

mammalian phenotype

References

Additional - Nkx2-1tm1.1(cre/ERT2)Zjh related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

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

Nkx2-1^{tm1.1(cre/ERT2)Zjh}

Allele Symbol: Nkx2-1^{tm1.1(cre/ERT2)Zjh}

Genotype: Nkx2-1^{tm1.1(cre/ERT2)Zjh}/Nkx2-1⁺
involves: 129S4/SvJae * C57BL/6

Additional - Nkx2-1^{tm1.1(cre/ERT2)Zjh} related