STOCK Ada^tm1Mw/J

Stock number: 002493
Product name: ADA KO
Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research

Description

These Ada knock-out mice exhibit perinatal lethality with and liver cell degeneration and defects in purine metabolism. They may be suitable for use in applications related to the study of severe combined immune deficiency in humans.

Detailed description

Mice homozygous for the Ada^tm1Mw targeted mutation die perinatally. They show defects in purine metabolism and have liver cell degeneration. Death is most likely the result of accumulation of ADA precursors. Mice from the double mutant strain FVB;129- Ada^tm1Mw-TgN(PLADA)4118Rkmb/J (Stock No. 003265) are rescued from embryonic lethality by transgenic ADA expression in the placenta. Rescued mice that are homozygous for the null Ada allele exhibit a severe combined immunodeficiency. In addition, mice develop a severe lung eosinopilia reminescent of that seen in humans with asthma. Abnormalities were also found in the bone and kidney. ADA deficient mice die from severe respiratory distress by three weeks of age. Mice carrying a transgene overexpressiong ADA in both the placenta and forestomach, FVB;129- Ada^tm1Mw-TgN(PLFSADA)2465Rkmb/J (Stock No. 003297), are rescued from postnatal lethality at three weeks of age. Rescued mice that are homozygous for the null Ada allele live a normal lifespan displaying only a partial immune deficiency and developing less severe pulmonary inflammation.

Allele

Symbol: Ada^tm1Mw
Name: targeted mutation 1, Maki Wakamiya
MGI accession ID: MGI:1857117
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ada
Marker name: adenosine deaminase
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt⁺
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.
General note: Phenotypic Similarity to Human Syndrome: Pulmonary Hypertension associated with Chronic Obstructive Pulmonary Disease J: 231559.