Strain background determines lymphoma incidence in Atm knockout mice.
About 10% to 30% of patients with ataxia-telangiectasia (A-T) develop leukemias or lymphomas. There is considerable interpatient variation in the age of onset and leukemia/lymphoma type. The incomplete penetrance and variable age of onset may be attributable to several factors. These include competing mortality from other A-T-associated pathologies, particularly neurodegeneration and interstitial lung disease, allele-specific effects of ataxia-telangiectasia mutated (ATM) gene mutations. There is also limited evidence from clinical observations and studies using Atm knockout mice that modifier genes may account for some variation in leukemia/lymphoma susceptibility. We have introgressed the Atm(tm1Awb) knockout allele (Atm(-)) onto several inbred murine strains and observed differences in thymic lymphoma incidence and latency between Atm(-/-) mice on the different strain backgrounds and between their F1 hybrids. The lymphomas that arose in these mice had a pattern of sequence gains and losses that were similar to those previously described by others. These results provide further evidence for the existence of modifier genes controlling lymphomagenesis in individuals carrying defective copies of Atm, at least in mice, the characterized Atm(-) congenic strain set provides a resource with which to identify these genes. In addition, we found that fewer than expected Atm(-/-) pups were weaned on two strain backgrounds and that there was no correlation between body weight of young Atm-/- mice and lymphoma incidence or latency.
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO.
Paula C
PC
Genik
Australian Infectious Diseases Research Centre, Queensland Institute of Medical Research, Australian School of Veterinary Science, University of Queensland, Gatton, Queensland, Australia.
Helle
H
Bielefeldt-Ohmann
Department of Environmental Health and Safety, Iowa State University, Ames, IA.
Xianan
X
Liu
Department of Radiation Oncology, Division of Molecular Radiation Biology and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.
Michael D
MD
Story
Department of Radiation Oncology, Division of Molecular Radiation Biology and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.
Lianghao
L
Ding
Department of Anatomic Pathology, IDEXX Laboratories, Inc, Westbrook, ME.
Jamie M
JM
Bush
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO.
Christina M
CM
Fallgren
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO. Electronic address: Michael.Weil@ColoState.EDU.
Michael M
MM
Weil
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015994:Incidence; D008223:Lymphoma / Q000235:genetics*; D008297:Male; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse