These double mutant mice carry a null allele of Ada and a transgene containing a murine cDNA minigene of Ada, founder line 2465. Transgenic ADA expression in the prenatal placenta and postnatal forestomach rescues the lethal phenotype of homozygous null mice, and the mice exhibit partial immune deficiency.
Dr. Michael R. Blackburn, Univ Texas Health Science Center
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Ada | adenosine deaminase |
Allele Type |
---|
Transgenic (Inserted expressed sequence) |
Mice homozygous for the Adatm1Mw targeted mutation die perinatally. They show defects in purine metabolism and develop liver cell degeneration. Death is most likely the result of accumulation of ADA precursors. In this strain (FVB;129-Adatm1Mw Tg(PLFSADA)2465Rkmb/J - Stock No. 003297), mice carry a transgene overexpressing ADA in both the placenta and forestomach. Double mutant mice homozygous for the null Ada allele live a normal lifespan displaying only a partial immune deficiency and developing less severe pulmonary inflammation.
Mice from the double mutant strain FVB,129- Adatm1Mw Tg(PLADA)4118Rkmb/J (Stock No. 003265) express ADA in the placenta alone. These mice are rescued from embryonic lethality, but die from severe respiratory distress by three weeks of age. These mice exhibit a severe combined immunodeficiency and develop a severe lung eosinopilia reminiscent of that seen in humans with asthma. Abnormalities are also found in the bone and kidney.
The original adenosine deaminase Ada knockout mice were generated by the insertion of the neomycin gene into exon 5 of the murine Ada gene. The targeting construct was electroporated into 129S7/SvEvBrd-derived AB1 embryonic stem (ES) cells.
This transgenic strain was made with a 36 bp deletion in the endogenous promoter directing Ada expression to the placenta and forestomach. The transgene was injected into the pronuclei of FVB/N mouse oocytes.
Expressed Gene | Ada, adenosine deaminase, mouse, laboratory |
---|---|
Site of Expression |
Allele Name | targeted mutation 1, Maki Wakamiya |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Ada-; adam1 |
Gene Symbol and Name | Ada, adenosine deaminase |
Gene Synonym(s) | |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 2 |
General Note | Phenotypic Similarity to Human Syndrome: Pulmonary Hypertension associated with Chronic Obstructive Pulmonary Disease J: 231559. |
Molecular Note | A neomycin selection cassette was inserted into exon 5. Activity assays demonstrated that no functional protein was made from this allele in homozygous mice. |
Mutations Made By | Dr. Maki Wakamiya, Baylor College of Medicine |
Allele Name | transgene insertion 2465, Michael R Blackburn |
---|---|
Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | Tg(Ada)2448Mw |
Gene Symbol and Name | Tg(PLFSADA)2465Rkmb, transgene insertion 2465, Michael R Blackburn |
Gene Synonym(s) | |
Promoter | Ada, adenosine deaminase, mouse, laboratory |
Expressed Gene | Ada, adenosine deaminase, mouse, laboratory |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | A construct was made that included a 2.8 kb genomic fragment containing the endogenous polyadenylation sequence, intron 11, and ~2kb of 3'-untranslated region and 3' flanking region of the gene. The endogenous promoter was replaced with a promoter containing a 36-bp deletion in the 5'-untranslated region. This resulted in a construct that contained the gene's regulatory elements, allowing expression in the placenta prenatally and the forestomach postnatally, while the 36-bp deletion in the promoter allowed distinction of this transcript from that of native transcript. RNase protection showed transgene transcript in placentas, but not fetuses, of transgenic animals. Enzymatic activity of the protein product was increased in the placenta, but not in the fetus, of transgenic mice compared to nontransgenic animals. |
Mutations Made By | Dr. Michael Blackburn, Univ Texas Health Science Center |
Mice homozygous for the Ada allele die just after birth. In this strain, expression of the transgene rescues the lethality phenotype, although homozygous null Ada mice display some immune deficiency. While maintaining a live colony, these mice are bred as heterozygous for the Ada allele and hemizygous for the transgene.
When using the ada
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Hemizygous or Non carrier for Tg(PLFSADA)2465Rkmb, Hemizygous or Non carrier forAda<tm1Mw> |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.