Phenotypes Associated with This Genotype

Genotype
MGI:8354855

• Allelic Composition: Calr^{tm1(CALR*)Argr}/Calr⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N * CBA/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hematopoietic system

increased hematopoietic stem cell proliferation ( J:262170 )

• the proportion of single HSCs that give rise to clones of more than 50 cells after 7 days in culture is higher and single HSCs show earlier cell division and form larger clones, however, the percentages of LSK, lineage-positive, Mac1+, CD41+, and CD71+ cells are unaltered

• while HSCs exhibit increased proliferation in vitro, the long-term in vivo repopulating activity of bone marrow cells in competitive bone marrow transplantation is normal

abnormal erythropoiesis ( J:262170 )

• mice treated with poly I:C exhibit compromised erythropoiesis in the bone marrow

extramedullary hematopoiesis ( J:262170 )

• a degree of extramedullary hematopoiesis is seen in some cases of poly I:C injected mice

abnormal bone marrow cell morphology/development ( J:262170 )

• mice treated with poly I:C exhibit an increase in megakaryopoiesis

• however, numbers of myeloerythroid progenitor populations and more mature myeloid cells (Mac1+ Ly6g+) in the bone marrow are not altered

increased megakaryocyte cell number ( J:262170 )

• bone marrow of poly I:C treated mice shows megakaryocytic hyperplasia, with megakaryocytes displaying large and hyperlobated nuceli and increased clustering

• no significant alternation in the proportion of megakaryocytes or myeloid cells is seen in the spleen

increased megakaryocyte progenitor cell number ( J:262170 )

• bone marrow of poly I:C contains increased numbers of colony-forming unit megakaryocytes

decreased erythroblast number ( J:262170 )

• bone marrow of poly I:C injected mice contains reduced numbers of CD71+Ter119+ erythroblasts

• however, no significant alternation in the proportion of erythroblasts is seen in the spleen

thrombocytosis ( J:262170 )

• mice induced with polyinosinic:polycytidylic acid (poly I:C) injection 6 to 8 weeks after birth develop thrombocytosis

• thrombocytosis is transplantable: wild-type recipient mice transplanted with bone marrow cells from heterozygous mice 2 months after poly I:C develop thrombocytosis and recipients also develop thrombocytosis after secondary transplantations

• platelets show normal response to several agonists including collagen-related peptide, thrombin, and adenosine 5-diphosphate

increased leukocyte cell number ( J:262170 )

• white blood cell counts are mildly elevated in some, but not all, cohorts of poly I:C treated mice

• however, red blood cell parameters are not affected

increased hematopoietic stem cell number ( J:262170 )

• bone marrow of poly I:C injected mice contains increased numbers of hematopoietic stem cells (HSCs), both Lin-Sca1+cKit+CD150+CD48- HSCs and E-SLAM HSCs (CD45+EPCR+CD150+CD48-)

immune system

increased leukocyte cell number ( J:262170 )

• white blood cell counts are mildly elevated in some, but not all, cohorts of poly I:C treated mice

• however, red blood cell parameters are not affected

cellular

increased hematopoietic stem cell proliferation ( J:262170 )

• the proportion of single HSCs that give rise to clones of more than 50 cells after 7 days in culture is higher and single HSCs show earlier cell division and form larger clones, however, the percentages of LSK, lineage-positive, Mac1+, CD41+, and CD71+ cells are unaltered

• while HSCs exhibit increased proliferation in vitro, the long-term in vivo repopulating activity of bone marrow cells in competitive bone marrow transplantation is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
essential thrombocythemia		DOID:2224	OMIM:187950 OMIM:601977 OMIM:614521	J:262170