Mice that are homozygous for this targeted mutation develop renal cysts, swollen alveoli and alveolar wall degradation. This mutant mouse strain may be useful in studies of polycystic kidney disease and emphysema.
Thomas L. Benjamin, Harvard Medical School
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Wwtr1 | WW domain containing transcription regulator 1 |
Mice that are homozygous for the targeted mutation are viable, fertile, small in size and less active than wildtype controls. Only 10-25% of the expected homozygotes are born. The Donating Investigator reports that breeding homozygous females successfully is uncommon and homozygotes usually succumb before breeding age. No gene product (protein) is detected by Western blot analysis. Homozygotes develop severe polycystic renal disease, with an onset as early as a few weeks of age, and emphysema, with swollen alveoli and breakdown of alveolar walls. Kidney size increases with age. Intestinal and pulmonary inflammation is observed in some homozygotes. Levels of protein polycystin 2 (PC2) is increased in kidney epithelial cells of homozygotes. Histological analysis reveals adipocytes are smaller than wildtype control.
A targeting vector containing the lacZ gene, neomycin resistance cassette and diphtheria toxin A chain selection cassette was used to disrupt exon 2, which encodes the first 144 amino acids. The construct was electroporated into 129S6/SvEv derived PluriStem 129/S6 Murine embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTAC mice and maintained on the same background by the Donating Investigator. Upon arrival at The Jackson Laboratory, the mice were crossed once to 129S1/SvImJ inbred mice (Stock No. 002448) to establish the colony.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression |
Allele Name | targeted mutation 1, Thomas Benjamin |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | TAZ- |
Gene Symbol and Name | Wwtr1, WW domain containing transcription regulator 1 |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 3 |
Molecular Note | Exon 2 was replaced with a SA-Betagal PGK-neo cassette such that the remaining open reading frame would be out of frame. Exon 2 encodes a 144 amino acid stretch containing the 14-3-3 binding domain and the WW domain. A western blot of protein extracts from mouse embryonic fibroblasts with a C-terminal antibody confirmed the absence of protein expression. |
Mutations Made By | Thomas Benjamin, Harvard Medical School |
When maintaining a live colony, these mice can be bred as heterozygotes. Only 10-25% of the expected homozygotes are born when heterozygotes are mate. The Donating Investigator reports that breeding homozygous females successfully is uncommon and homozygotes usually succumb before breeding age.
When using the 129S-Wwtr1tm1Benj/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #011120 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
heterozygous or wildtype for Wwtr1<tm1Benj> |
Frozen Mouse Embryo | 129S-Wwtr1<tm1Benj>/J | $2595.00 |
Frozen Mouse Embryo | 129S-Wwtr1<tm1Benj>/J | $2595.00 |
Frozen Mouse Embryo | 129S-Wwtr1<tm1Benj>/J | $3373.50 |
Frozen Mouse Embryo | 129S-Wwtr1<tm1Benj>/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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