Atm haploinsufficiency results in increased sensitivity to sublethal doses of ionizing radiation in mice (original) (raw)

Nature Genetics volume 21, pages 359–360 (1999)Cite this article

Patients with the recessive disease ataxia telangiectasia1 (AT) and _Atm_-deficient mice2,3,4 have much reduced lifespans due in part to cancer susceptibility, and are extremely sensitive to ionizing radiation (IR). In contrast, it is uncertain whether AT carriers display reduced lifespan, cancer susceptibility or increased sensitivity to the effects of IR. We have addressed this question using a mouse model of AT. When wild-type (Atm+/+) mice or littermates heterozygous for a null allele of Atm (Atm +/–) were exposed to sublethal doses of IR, Atm +/– carriers displayed increased sensitivity to IR manifested by decreased survival and premature greying.

Atm+/+ and Atm +/– littermates were generated by outcrossing germline-transmitting _Atm_-deficient chimaeras (allele designation Atm tm1Awb) to NIH Black Swiss mice (F1, in which all mice have identical 50:50 129/SvEv:NIH Black Swiss backgrounds), or from F1 heterozygous crosses of similar genetic background, and genotyped by Southern-blot analysis2. Adult wild-type and Atm+/- littermates of 2-4 months of age were treated with 4 Gy of IR and monitored for illness and survival. We performed autopsies on all but eight animals (which had significant autolysis, were cannibalized, or were discarded mistakenly by caretakers). The time of death was determined within one week, as a weekly census was taken of all animals.

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Figure 1: Effects of IR on longevity and coat greying.

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Acknowledgements

We thank D. Larson and T. Hernandez for technical assistance, S. Hoogstraten-Miller for veterinary care and S. Abshire and N. Grey for mouse caretaking.

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Author notes

  1. Carrolee Barlow
    Present address: The Salk Institute for Biological Sciences, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA
  2. Anthony Wynshaw-Boris
    Present address: UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California, 92093, USA

Authors and Affiliations

  1. Genetic Disease Research Branch, National Human Genome Research Institute,
    Carrolee Barlow & Anthony Wynshaw-Boris
  2. Veterinary Resources Program, Office of Research Services, Office of the Director, National Institutes of Health, Bethesda, 20892, Maryland, USA
    Michael A. Eckhaus
  3. Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, 21224, Maryland, USA
    Alejandro A. Schäffer

Authors

  1. Carrolee Barlow
  2. Michael A. Eckhaus
  3. Alejandro A. Schäffer
  4. Anthony Wynshaw-Boris

Corresponding author

Correspondence toAnthony Wynshaw-Boris.

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Barlow, C., Eckhaus, M., Schäffer, A. et al. Atm haploinsufficiency results in increased sensitivity to sublethal doses of ionizing radiation in mice.Nat Genet 21, 359–360 (1999). https://doi.org/10.1038/7684

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