These IRlox mutant mice have loxP sites flanking exon 4 of the targeted gene. When bred to Cre-recombinase expressing mice, offspring will have a deletion of exon 4 in the cre expressing tissue(s). These floxed mice may be useful in studying insulin receptor function in several different tissues (including pancreas, liver, and skeletal muscle), as well as diabetes and glucose regulation.
C. Ronald Kahn, Joslin Diabetes Center
Mice homozygous for this IRlox allele are viable and fertile. These mutant mice have loxP sites flanking exon 4 of the targeted gene. When bred to Cre-recombinase expressing mice, offspring will have a deletion of exon 4 in the cre expressing tissue(s). These "floxed" mice may be useful in studying insulin receptor function in several different tissues (including pancreas, liver, and skeletal muscle), as well as diabetes and glucose regulation.
For example, when crossed to a strain expressing Cre recombinase in the central and peripheral nervous system (see Stock No. 003771), this mutant mouse strain may be useful in studies of glucose homeostasis.
When crossed to a strain expressing Cre recombinase in skeletal and cardiac muscle (see Stock No. 006475), this mutant mouse strain may be useful in studies of diabetes.
When crossed to a strain expressing Cre recombinase in the liver (see Stock No. 003574), this mutant mouse strain may be useful in studies of insulin resistance.
When crossed to a strain expressing Cre recombinase in pancreatic beta cells (see Stock No. 003573), this mutant mouse strain may be useful in studies of diabetes.
A targeting vector was designed to insert a loxP-flanked neomycin cassette downstream of exon 4, as well as a single loxP site 80 bp downstream of exon 4 of the targeted gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. ES cell were transiently transfected with a Cre-recombinase plasmid to delete the selection cassette, leaving single loxP sites upstream and downstream of exon 4. Correctly targeted ES cells were injected into C57BL/6J blastocysts, which were injected into pseudopregnant CD-1 foster females. The resulting mutant mice (IRlox) were backcrossed to C57BL/6J inbred mice. At some point, mice were bred to Mck-Cre transgenic mice (FVB genetic background, see Stock No. 006405). The double mutants were backcrossed for 10 generations to C57BL/6 mice and then selected for the IRlox (and against the transgene) prior to arrival at The Jackson Laboratory.
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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Ronald Kahn|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Insrflox; IR(lox); IRflox; IRLox; IRlox|
|Gene Symbol and Name||Insr, insulin receptor|
|Strain of Origin||129S4/SvJae|
|General Note||In conjunction with Tg(Mycha-cre)1Abel, this allele is knocked out specifically in cardiac muscle. The resulting mice are referred to as "Cardiac-specific insulin receptor knockout mice" or CIRKO. |
In conjunction with Tg(Ckmm-cre)5Khn, this allele is disrupted specifically in skeletal muscle. The resulting mice are referred to as "Muscle-specific insulin receptor knockout mice" or MIRKO.
|Molecular Note||Exon 4 was left flanked by single loxP sites after a downstream floxed neo cassette was removed via in vitro cre mediated recombination. Deletion of the resultant floxed fragment will result in a frameshift mutation that introduces a stop codon. Translation, if it were to occur, would putatively produce a truncated peptide consisting of 308 amino terminal residues and lacking the high affinity binding site, transmembrane domain, and kinase domain.|
|Mutations Made By|| |
C. Ronald Kahn, Joslin Diabetes Center
When maintaining a live colony, homozygous mice are bred.
When using the IRLox mouse strain in a publication, please cite the originating article(s) and include JAX stock #006955 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.