Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia

@article{Barlow1996AtmDeficientMA,
  title={Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia},
  author={Carrolee Barlow and Shinji Hirotsune and Richard E Paylor and Marek Liyanage and Michael A. Eckhaus and Francis S. Collins and Yosef Shiloh and Jacqueline N. Crawley and Thomas Ried and Danilo A Tagle and Anthony Wynshaw-Boris},
  journal={Cell},
  year={1996},
  volume={86},
  pages={159-171}
}
A murine model of ataxia telangiectasia was created by disrupting the Atm locus via gene targeting. Mice homozygous for the disrupted Atm allele displayed growth retardation, neurologic dysfunction, male and female infertility secondary to the absence of mature gametes, defects in T lymphocyte maturation, and extreme sensitivity to gamma-irradiation. The majority of animals developed malignant thymic lymphomas between 2 and 4 months of age. Several chromosomal anomalies were detected in one of… Expand
Pleiotropic defects in ataxia-telangiectasia protein-deficient mice.
  • A. Elson, Y Wang, +4 authors P. Leder
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1996
TLDR
It is demonstrated that the Atm protein exists as two discrete molecular species, and that loss of one or of both of these can lead to the development of the disease. Expand
Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice
TLDR
Reducing homologous recombination through genetic deletion of the Rad52 protein was able to decrease substantially the development of T-cell lymphomas in Atm−/− mice, resulting in an increased life span of the double mutant mice. Expand
Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer.
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  • Biology, Medicine
  • Biochemical and biophysical research communications
  • 2014
TLDR
The gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies. Expand
Atm reactivation reverses ataxia telangiectasia phenotypes in vivo
TLDR
A new Atm mouse model is proposed to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease and life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Expand
Multiple ATM-dependent pathways: an explanation for pleiotropy.
TLDR
The hallmark features of AT are degenerative neurological function, particularly in the cerebellum, and oculocutaneous telangiectasias, often accompanied by immunodeficiency, infertility, small size, sensitivity to the effects of ionizing radiation, and increased predisposition to cancer. Expand
Ataxia telangiectasia.
  • T. Crawford
  • Biology, Medicine
  • Seminars in pediatric neurology
  • 1998
TLDR
Newly produced ATM-deficient transgenic mice express most of the cellular features of the disorder but have yet to mimic the distinctive neurodegeneration. Expand
Partial rescue of the prophase I defects of Atm-deficient mice by p53 and p21 null alleles
TLDR
It is demonstrated that male gametogenesis is severely disrupted in Atm-deficient mice in the earliest stages of meiotic prophase I, resulting in apoptotic degeneration. Expand
Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9 null mice.
TLDR
The characteristics of the Fancg(-/-) mice closely resemble those reported for Fancc and Fanca null mice, supporting a tight interdependence of the corresponding gene products in a common pathway. Expand
Bone marrow transplantation restores immune system function and prevents lymphoma in Atm-deficient mice.
TLDR
It is shown that the replacement of the bone marrow compartment in Atm knockout mice (Atm(-/-)) using a clinically relevant, nonmyeloablative host-conditioning regimen can be used to overcome the immune deficiencies and prevent the malignancies observed in these mice. Expand
Atm heterozygous deficiency enhances development of mammary carcinomas in p53 heterozygous knockout mice
IntroductionAtaxia-telangiectasia is an autosomal-recessive disease that affects neuro-immunological functions, associated with increased susceptibility to malignancy, chromosomal instability andExpand
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TLDR
Molecular characterization of rearrangements specific to T-lymphocytes suggests that a DNA repair/processing defect is potentially responsible for the diverse array of chromosomal abnormalities observed in a variety of AT cell types. Expand
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TLDR
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TLDR
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