Phox2b-Cre BAC transgenic mice have Cre recombinase expression directed primarily to the hindbrain by the Phox2b promoter/enhancer regions, and may be used to generate conditional mutations for studying neuronal cell types expressing or depending on the Phox2b transcription factor. Specifically, these mice may be useful for studying human respiratory disease, central chemoreceptive neurons in the retrotrapezoid nucleus, respiratory rhythmogenesis, and autonomic nervous system dysregulation (such as congenital central hypoventilation syndrome (CCHS) or Ondine-Hirschsprung disease).
Joel K Elmquist, UT Southwestern Med Center at Dallas
Genetic Background | Generation |
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N12+N1F8
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Allele Type |
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Transgenic (Recombinase-expressing) |
Starting at:
$278.00 Domestic price for female 4-week |
356.51 Domestic price for breeder pair |
Phox2b-Cre BAC transgenic mice are viable and fertile, with Cre recombinase expression under control of the Phox2b promoter/enhancer regions within the BAC transgene. cre-expressing neurons co-express PHOX2B (as shown by in situ hybridization). Phox2b-Cre BAC transgenic mice from founder line 3 exhibit cre expression directed primarily to the hindbrain; specifically the dorsal motor nucleus of the vagus (DMV) in parasympathetic visceral and branchial motor neurons, nodose sensory ganglia, and nucleus of the solitary tract (NTS) cells. No transgene expression is reported in hypothalamus or spinal cord. Although endogenous Phox2b expression is reported in peripheral ganglia along with the enteric nervous system, no peripheral transgene expression is reported for these Phox2b-Cre BAC transgenic mice. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequences in the offspring. These Phox2b-Cre BAC transgenic mice may be used to generate conditional mutations for studying neuronal cell types expressing/depending on the Phox2b transcription factor for energy balance, glucose homeostasis, and autonomic breathing/respiration. Specifically, these mice may be useful for studying human respiratory disease, central chemoreceptive neurons in the retrotrapezoid nucleus, respiratory rhythmogenesis, and autonomic nervous system dysregulation (such as congenital central hypoventilation syndrome (CCHS) or Ondine-Hirschsprung disease).
For example, when Phox2b-Cre BAC transgenic mice are bred with floxed leptin receptor mice (Stock No. 008327), the resulting offspring allow studying hindbrain nucleus of the solitary tract (NTS) leptin receptor function in NTS appetite, hunger, and food consumption.
The Phox2b-Cre BAC transgene was designed in the laboratory of Dr. Joel K. Elmquist (University of Texas Southwestern Medical Center at Dallas). The C57BL/6J mouse bacterial artificial chromosome (BAC) RP24-95M11, containing the entire Phox2b locus was obtained. This BAC also contained ~130kb sequence upstream of the Phox2b locus (including part of the Limch1 locus) and ~70kb of sequence downstream of the Phox2b locus. A Cre recombinase sequence fused with an frt-flanked neomycin gene was inserted into the ATG start site of the Phox2b locus on the RP24-95M11 BAC via homologous recombination/BAC recombineering. The frt-flanked neo was removed via transient transfection of an FLP-expressing vector during BAC recombineering. The resulting ~200 kb Phox2b-Cre BAC transgene was injected into C57BL/6J mouse pronuclei to produce independent founder lines. Transgenic founders were bred with ROSA-lacZ mice (on a mixed B6;129- or C57BL/6-congenic background; see Stock Nos. 003309 or 003474). Founder line 3 was found with the greatest degree of nucleus of the solitary tract (NTS) cells expressing Cre recombinase. Mice from founder line 3 were subsequently backcrossed to C57BL/6J mice for at least ten generations (and the ROSA-lacZ mutation removed) prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
In 2017, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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. One of the 43 markers, at the thymus cell antigen 1, theta (Thy1) gene was segregating.
Expressed Gene | cre, cre recombinase, bacteriophage P1 |
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Site of Expression | cre expression is directed primarily to the hindbrain; specifically the dorsal motor nucleus of the vagus in parasympathetic visceral and branchial motor neurons, nodose sensory ganglia, and nucleus of the solitary tract cells. |
Allele Name | transgene insertion 3, Joel K Elmquist |
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Allele Type | Transgenic (Recombinase-expressing) |
Allele Synonym(s) | |
Gene Symbol and Name | Tg(Phox2b-cre)3Jke, transgene insertion 3, Joel K Elmquist |
Gene Synonym(s) | |
Promoter | Phox2b, paired-like homeobox 2b, mouse, laboratory |
Expressed Gene | cre, cre recombinase, bacteriophage P1 |
Site of Expression | cre expression is directed primarily to the hindbrain; specifically the dorsal motor nucleus of the vagus in parasympathetic visceral and branchial motor neurons, nodose sensory ganglia, and nucleus of the solitary tract cells. |
Strain of Origin | C57BL/6J |
Chromosome | UN |
Molecular Note | The mouse BAC RP24-95M11, containing the entire Phox2b locus and 130kb sequence upstream of the Phox2b locus (including part of the Limch1 locus) and 70kb of sequence downstream of the Phox2b locus was modified to produce the construct. A Cre recombinase sequence fused with an frt-flanked neomycin gene was inserted into the ATG start site of the Phox2b locus via homologous recombination/BAC recombineering. The frt-flanked neo was removed via transient transfection of an FLP-expressing vector during BAC recombineering. The resulting ~200 kb Phox2b-Cre BAC transgene was injected into C57BL/6J mouse pronuclei to produce independent founder lines. Founder line 3 was found with the greatest degree of nucleus of the solitary tract (NTS) cells expressing Cre recombinase. |
Mutations Made By | Joel Elmquist, UT Southwestern Med Center at Dallas |
When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) mice from the colony or to C57BL/6J inbred mice (Stock No. 000664).
When using the Phox2b-Cre line 3 mouse strain in a publication, please cite the originating article(s) and include JAX stock #016223 in your Materials and Methods section.
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(Phox2b-cre)3Jke |
Frozen Mouse Embryo | B6(Cg)-Tg(Phox2b-cre)3Jke/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6(Cg)-Tg(Phox2b-cre)3Jke/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6(Cg)-Tg(Phox2b-cre)3Jke/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6(Cg)-Tg(Phox2b-cre)3Jke/J Frozen Embryo | $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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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