Homozygous females and hemizygous males have increased resistance to corneal and pulmonary infection, and have altered immune, hematopoietic, and vascular permeability. Mice with this X-linked targeted mutation may be useful in studies of cornea and pulmonary infection, pulmonary injury and aneurysm, and antibiotic-resistant pulmonary infections, such as those often observed in cystic fibrosis patients.
Paul D. Soloway, Cornell University
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Timp1 | tissue inhibitor of metalloproteinase 1 |
Homozygous females and hemizygous males (the gene is X-linked) are viable and fertile. No endogenous transcript is detected in lung tissue from affected mice by Northern blot analysis.. Homozygous mice have increased resistance to corneal and pulmonary infection with P. aeruginosa, and have altered immune, hematopoietic, and vascular permeability in bleomycin-induced lung injury trials. Homozygotes also show increased and continued progression of aneurysm formation compared with wild-type mice in induced thoracic aortic aneurysm (TAA) models. Mice with this X-linked targeted mutation may be useful in studies of cornea and pulmonary infection, pulmonary injury and aneurysm, as well as of P. aeruginosa resistance in individuals with unresolved, antibiotic-resistant pulmonary infections, such as those often observed in cystic fibrosis patients.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. Mice with this mutation have been published on many different genetic backgrounds. It should be noted that the phenotype could vary from that originally described. We will modify the strain description as published results become available.
A targeting vector was designed to insert a neomycin resistance cassette into exon 3 of the endogenous gene on the X chromosome. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The donating investigator reported that the resulting mutant mice were backcrossed to C57BL/6 inbred mice (see SNP note below) for more than 12 generations before arriving 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, at least 2 of 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 mixed C57BL/6J ; C57BL/6N genetic background.
Allele Name | targeted mutation 1, Paul D Soloway |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | TIMP-1-; Timp1-; Timp1tm1Jae; TIMP1KO; TIMP-1KO |
Gene Symbol and Name | Timp1, tissue inhibitor of metalloproteinase 1 |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | X |
Molecular Note | Insertion of a neomycin-thymidine kinase expression cassette resulted in a duplication of part of the gene (the second through the fifth coding exons, with the duplicated copies separated by the selectable markers), and inserted into the third coding exon a 21 bp sequence that placed a stop codon in each reading frame. Northern blot analyses failed to detect transcripts from this allele in lung, ovaries or embryonic fibroblasts. |
Mutations Made By | Paul Soloway, Cornell University |
When maintaining a live colony, homozygous females are bred to hemizygous males.
When using the Timp1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006243 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
X linked - Heterozygous females and Wild-type Males for Timp1<tm1Pds> |
Frozen Mouse Embryo | B6.129S4-Timp1<tm1Pds>/J | $2595.00 |
Frozen Mouse Embryo | B6.129S4-Timp1<tm1Pds>/J | $2595.00 |
Frozen Mouse Embryo | B6.129S4-Timp1<tm1Pds>/J | $3373.50 |
Frozen Mouse Embryo | B6.129S4-Timp1<tm1Pds>/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. 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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