These Foxa2loxp/loxp mutant mice possess loxP sites flanking exon 3 of the forkhead box A2 (Foxa2) gene. This strain may be useful for studying the role of HNF3β on embryonic development and metabolism regulation.
Klaus H. Kaestner, University of Pennsylvania
These Foxa2loxp/loxp mutant mice possess loxP sites flanking exon 3 of the forkhead box A2 (Foxa2) gene. Also known as hepatocyte nuclear factor 3 β (HNF3β), FOXA2 is a transcription factor involved in embryonic development, cellular differentiation, and gene expression during liver, pancreas and lung development. FOXA2 plays a role in glucose homeostasis and fat metabolism. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in cre-expressing tissues.
For example, when crossed to B6.Cg-Tg(Ins2-cre)25Mgn/J mice
(Stock No. 003573) expressing Cre recombinase in pancreatic beta cells, double mutant mice exhibit abnormal islet and beta cell morphology and decreased glucagon secretion. They also have elevated glycogen and insulin levels.
When crossed to B6.Cg-Tg(SFTPC-rtTA)5Jaw/J
(Stock No. 006235) and B6.Cg-Tg(tetO-cre)1Jaw/J (Stock No. 006234) mice with doxycycline inducible Cre recombinase expression under the indirect control of the human SFTPC, surfactant, pulmonary-associated protein C, promoter, triple mutant mice develop severe pulmonary distress on the first day of life similar to respiratory distress syndrome in preterm infants.
When crossed to B6.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
(Stock No. 006232) and B6.Cg-Tg(tetO-cre)1Jaw/J (Stock No. 006234) mice with doxycycline inducible Cre recombinase expression under the indirect control of the rat secretoglobulin (uteroglobulin) promoter (expression in respiratory epithelial cells), triple mutant mice develop airspace enlargement, goblet cell hyperplasia and increased mucin and neutrophilic infiltration in lungs.
A targeting vector was designed to insert a loxP site upstream of exon 3, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 3 of the forkhead box A2 (Foxa2) gene. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a pIC-Cre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exon 3, intact floxed-neo cassette, or excision of both exon 3 and the neo cassette. Correctly targeted ES cells, containing only the floxed-exon 3, were injected into C57BL/6J blastocysts and resulting chimeric males were bred with C57BL/6 females. Resulting offspring were bred to CD-1 mice and were subsequently bred to C57BL/6 mice for at least 5 generations. 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. Nine of 27 markers throughout the genome, as well as 5 of 5 markers that determine C57BL/6J from C57BL/6N, were found to be segregating. Two markers were from an unknown source. This suggests a contamination from an unknown source or incomplete backcross.
|Allele Name||targeted mutation 1, Klaus H Kaestner|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Foxa2flox; Foxa2loxP; HNF3betaflox|
|Gene Symbol and Name||Foxa2, forkhead box A2|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A single loxP site was inserted into intron 2 and a loxP flanked neomycin and thymidine kinase selection cassette was inserted into intron 3. The selection cassette was removed in ES cells by transient Cre expression prior to the production of chimeric mice, leaving exon 2 flanked by loxP sites in the final allele.|
When maintaining a live colony mice homozygous for the floxed allele may be bred together.
When using the HNF3βloxP mouse strain in a publication, please cite the originating article(s) and include JAX stock #022620 in your Materials and Methods section.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.