Sci. Aging Knowl. Environ., 3 October 2001
Vol. 2001, Issue 1, p. tg3


atm-/- Strain 3;2001/1/tg3

Mouse atm-/- Strain 3
Genetic background 129/SvEv x Black Swiss
Gene changed Atm (Different authors cite the mouse ATM as ATM, Atm, or atm.)
Type of change Truncation mutation (disruption of the sequence at the position corresponding to nucleotide 5460 of human ATM)
Nature of protein A 370-kD member of the phosphatidylinositol 3-kinase (PI3-K)--related kinases (PIKK). It has a C-terminal sequence with significant homology to the catalytic domain of PI3-K and an adjacent domain related to the checkpoint gene rad-3. ATM has intrinsic protein kinase activity. No measurable lipid kinase function has yet been shown. ATM's substrates include p53, p95/NBS1, MDM2, and CHK2.
Phenotype Smaller size and lower weight than wild-type or heterozygote littermates that is most striking at birth and at weaning (19 to 21 days), but remains quite obvious when entering adulthood (38-42 days); 6.5-fold increase in chromosomal breakage per metaphase (in otherwise untreated cells) over wild-type or heterozygote mice; absence of mature sperm; increase in CD4+ CD8+ thymocyte numbers together with a 4-fold decrease in mature CD4+ thymocytes; 2- to 3-fold decrease in the number of cells with Thy-1, CD3, {alpha}{beta} TCR, CD4, or CD8 markers in the spleen; lack of significant changes in the proportion of cells expressing B220 or IgM; development of malignant thymoma between 3 and 4 months of age; a significantly higher occurrence of apoptosis of unirradiated thymocytes during in vitro incubation compared to control cells, similar extent of apoptosis by a given dose of ionizing radiation in knockout and control thymocytes.
Corresponding human phenotype Ataxia telangiectasia (AT) is an autosomal recessive disorder presenting in childhood and characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia and variable immunodeficiency involving the function of both B and T lymphocytes. Chromosomal instability, increased sensitivity to ionizing radiation, a high incidence of hematolymphoid malignancies, growth retardation, incomplete sexual maturation, endocrine deficits and premature aging of the skin and hair are other salient features of the disease.
Primary reference A. Elson, Y. Wang, C.J. Daugherty, C.C. Morton, F. Zhou, J. Campos-Torres, P. Leder, Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Proc. Natl. Aca. Sci. U.S.A. 93, 13084-13089 (1996).
Additional references See below.
Source Authors of primary reference.
Other comments While the 3 different atm knockout mice display very similar phenotypes, the following discrepancies exist:
1. Low animal weight is not perceived at the same time in the 3 knockouts.
2. B cell numbers are deemed normal in some groups, but not others (which in itself is consistent with the phenotypes of humans with the disease).
Other links Related transgenic/knockout mice:
atm-/- Strain 1:;2001/1/tg1
atm-/- Strain 2:;2001/1/tg2
SAGE KE's Genes/Interventions database:;207
Keywords Ataxia telangiectasia, atm, phosphatidylinositol 3-kinase, lymphocytes, malignancy, p53
Prepared by Amir A. Sadighi Akha

October 3, 2001

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