Strain background determines lymphoma incidence in Atm knockout mice.

Abstract:

: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.

journal_name

Neoplasia

authors

Genik PC,Bielefeldt-Ohmann H,Liu X,Story MD,Ding L,Bush JM,Fallgren CM,Weil MM

doi

10.1593/neo.131980

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

129-36

issue

2

eissn

1522-8002

issn

1476-5586

pii

S1476-5586(14)80012-2

journal_volume

16

pub_type

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