FVB;129-Ada^tm1Mw Tg(PLADA)4118Rkmb/J

Stock number: 003265
Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research

Description

These double mutant mice carry a null allele of Ada and a transgene containing a murine cDNA minigene of Ada, founder line 4118, and exhibit partial immune deficiency. Transgenic ADA expression in the placenta rescues the lethal phenotype of homozygous null mice.

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 Tg(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 eosinophilia 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 Tg(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: Tg(PLADA)4118Rkmb
Name: transgene insertion 4118, Michael R Blackburn
MGI accession ID: MGI:2683027
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(PLADA)4118Rkmb
Marker name: transgene insertion 4118, Michael R Blackburn
Chromosome: UN
Strain of origin: Not Specified
Expressed genes: Ada,adenosine deaminase,mouse, laboratory
Molecular note: A construct was made that contained the endogenous polyadenylation sequence, intron 11, and ~2kb of of the 3' flanking region of the gene. The endogenous promoter was replaced with a promoter containing a 36-bp deletion in the 5'-untranslated region and 770-bp trophoblast regulatory element. This resulted in a construct that allowed expression in the placenta prenatally only, while the 36-bp deletion in the promoter allowed distinction of this transcript from that of native transcript. Enzymatic activity of the protein product was not detected in any of the tissues tested at postnatal day 17 in transgenic mice.

Allele

Symbol: Ada^tm1Mw
Name: targeted mutation 1, Maki Wakamiya
MGI accession ID: MGI:1857117
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Ada-; ada^m1
Marker symbol: Ada
Marker name: adenosine deaminase
Marker synonyms: ADA1
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
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.