Mouse Genome Informatics
ht
    Crebbptm1Dli/Crebbp+
involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
growth/size

craniofacial
• craniofacial abnormalities

tumorigenesis
• hematologic neoplasia in animals 1 year or older, which include histiocytic sarcomas, a tumor of hematopoietic origin, and myelogenous and lymphocytic leukemias
• myelogenous and lymphocytic leukemias

hematopoietic system
• increase in myeloid cells in mice with splenomegaly (J:60630)
• abundance of all hematopoietic cells types is significantly diminished in mice with splenomegaly (J:60630)
• 2 of 14 mice at 3-4 months of age have small clusters of immature cells in the center of the marrow space, indicative of very early stages of myelodysplastic hematopoiesis (J:191503)
• mutants show an increase in Annexin V+ cells in the lineage-depleted (Lin-) fraction of the marrow enriched for stem and progenitor cells, indicating an increase in apoptosis in marrow progenitors
• in mice with splenomegaly (J:60630)
• mutants have fewer total colony-forming cells in the marrow than wild-type mice, most notably the granulocytic and monocytic colony-forming cells (J:191503)
• 9-12 month old mutants show a decrease in common myeloid progenitors (J:191503)
• 22% of 9-12 month old mutants show leukocytes with a pseudo Pelger-Huet anomaly
• lymphoid cell compartment is smaller at 9-12 months of age
• however, leukocyte, erythrocyte and platelet numbers are normal
• in mice with splenomegaly
• in mice with splenomegaly
• 55% of 9-12 month old mutants show hypersegemented granulocytes
• at 9-12 months of age
• in mice with splenomegaly
• bone marrow is more cellular than in wild type mice when corrected for body weight at 3-4 and 9-12 months of age
• more than 50% of 9-12 month old mutants exhibit either increased numbers of megakaryocytes or abnormal forms such as hyperlobulated cells or naked nuclei
• approximate 2-fold fewer long-term hematopoietic stem cells per femur at 9-12 months of age
• severe splenomegaly in 73% of 12-18 month old mice but not in young mice (J:60630)
• spleen contains an excess of myeloid and erythroid cells (J:60630)
• mild but significant splenomegaly in 3-4 and 9-12 month old mutants (J:191503)

immune system
• 22% of 9-12 month old mutants show leukocytes with a pseudo Pelger-Huet anomaly
• lymphoid cell compartment is smaller at 9-12 months of age
• however, leukocyte, erythrocyte and platelet numbers are normal
• in mice with splenomegaly
• in mice with splenomegaly
• 55% of 9-12 month old mutants show hypersegemented granulocytes
• at 9-12 months of age
• severe splenomegaly in 73% of 12-18 month old mice but not in young mice (J:60630)
• spleen contains an excess of myeloid and erythroid cells (J:60630)
• mild but significant splenomegaly in 3-4 and 9-12 month old mutants (J:191503)

cellular
• mutants treated with a 10-Gy split-dose total body irradiation die before wild-type mice do and none survive compared to 1/3 of wild-type mice that survive, indicating increased hypersensitivity to ionizing radiation
• a lower percentage of mutants treated with a split-dose of 11 Gy total body irradiation followed by a bone marrow graft survive compared to wild-type mice treated in the same way

Mouse Models of Human Disease
OMIM IDRef(s)
Leukemia, Acute Myeloid; AML 601626 J:60630
Myelodysplastic Syndrome; MDS 614286 J:191503
Rubinstein-Taybi Syndrome 1; RSTS1 180849 J:60630