Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP.
Mice with monoallelic inactivation of the CBP gene develop highly penetrant, multilineage defects in hematopoietic differentiation and, with advancing age, an increased incidence of hematologic malignancies. The latter are characterized, at least in some cases, by loss of heterozygosity (LOH) at the CBP locus. No such pathology was observed in wild-type or p300 heterozygous null mice of the same age and genetic background. Thus, a full complement of CBP, but not p300, is required for normal hematopoietic differentiation. These results also provide the first experimental evidence for the hypothesis that CBP has tumor-suppressing activity.
Kung
A L
AL
Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Rebel
V I
VI
Bronson
R T
RT
Ch'ng
L E
LE
Sieff
C A
CA
Livingston
D M
DM
Yao
T P
TP
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D050882:CREB-Binding Protein; D017690:Cell Transplantation; D050881:E1A-Associated p300 Protein; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology; D006410:Hematopoiesis / Q000235:genetics*; D006579:Heterozygote; D019656:Loss of Heterozygosity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
D009687:Nuclear Proteins; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse