This Smad4 knock-out strain is useful in studies of TGF-beta signaling and embryonic development.
Dr. Tak Mak, University Health Network/Un of Toronto
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Smad4 | SMAD family member 4 |
The targeted Smad4 gene encodes a signal transduction critical to TGF-beta signaling and embryonic development. Mutations in this gene have been associated with human pancreatic carcinoma, Juvenile Polyposis Syndrome, Hereditary Hemorrhagic Telangiectasia Syndrome, and Myhre Syndrome. These knock-out mice carry a mutation in which exon 8 and part of exon 9 have been replaced by a NEO selection cassette. No gene product (protein) is detected by Western blot analysis of homozygous immortalized embryonic fibroblasts. Homozygous null mice have an embryonic lethal phenotype, failing to gastrulate or develop past embryonic day 7.5. A decrease in embryo size is observed at E5.5, with disorganized and poorly defined embryonic and the extraembryonic regions. Decreased cell proliferation is detected in homozygous embryos at E6.5 by BrdU labeling. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background. Mice that are heterozygous for the targeted mutation are viable and fertile.
A targeting vector containing a floxed PGK-NEO cassette was used to disrupt exon 8 and part of exon 9. The construct was electroporated into 129P2/OlaHsd derived E14K embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were bred to C57BL/6 to achieve germline transmission. The mice were then backcrossed to C57BL/6 for 9 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background. Upon arrival, sperm was cryopreserved.
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. While the 43 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, Tak Mak |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Smad4tm1Ari |
Gene Symbol and Name | Smad4, SMAD family member 4 |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 18 |
Molecular Note | A neomycin resistance cassette replaced exon 8 and part of exon 9 of the gene. |
When maintaining a live colony, heterozygous mice may be bred to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). Homozygotes are not viable (embryonic lethal).
When using the Smad4 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #029250 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Smad4<tm1Mak> |
Frozen Mouse Embryo | B6.129P2-Smad4<tm1Mak>/J | $2595.00 |
Frozen Mouse Embryo | B6.129P2-Smad4<tm1Mak>/J | $2595.00 |
Frozen Mouse Embryo | B6.129P2-Smad4<tm1Mak>/J | $3373.50 |
Frozen Mouse Embryo | B6.129P2-Smad4<tm1Mak>/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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