Irradiated Blm-deficient mice are a highly tumor prone model for analysis of a broad spectrum of hematologic malignancies.
Mutations in the BLM gene cause human Bloom syndrome (BS), an autosomal recessive disorder of growth retardation, immunodeficiency and cancer predisposition. Homozygous null Blm(m3/m3) mice are cancer prone with a 5-fold increased risk of cancer compared with Blm(m3/+) and Blm(+/+) mice. Irradiation of Blm(m3/m3) mice increased the risk to 28-fold. Tumors occurred mainly in the hematopoietic system and were similar to those in BS based on detailed histologic and immunohistochemical analyses. Irradiated Blm-deficient mice thus provide a novel model for understanding accelerated malignancies in BS and a new platform for investigating the molecular basis for a wide range of hematopoietic neoplasms.
Warren
Madhuri
M
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. mvw@pathologydiagnostics.com
Chung
Yeun-Jun
YJ
Howat
William J
WJ
Harrison
Hannah
H
McGinnis
Ralph
R
Hao
Xingpei
X
McCafferty
John
J
Fredrickson
Torgny N
TN
Bradley
Allan
A
Morse
Herbert C
HC
D000818:Animals; D001816:Bloom Syndrome / Q000150:complications; D004195:Disease Models, Animal; D019337:Hematologic Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D053484:RecQ Helicases / Q000172:deficiency*
C097151:Bloom syndrome protein; D053484:RecQ Helicases