Phenotypes Associated with This Genotype

Genotype
MGI:8354856

• Allelic Composition: Calr^{tm1(CALR*)Argr}/Calr^{tm1(CALR*)Argr}; 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

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

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

increased common myeloid progenitor cell number ( J:262170 )

• myeloid progenitors (Lin-Sca1-cKit+) are expanded in poly I:C treated mice

decreased bone marrow cell number ( J:262170 )

• by 6-7 months after poly I:C, mice show reduced bone marrow cellularity and bone marrow is paler

increased granulocyte monocyte progenitor cell number ( J:262170 )

• pre-granulocyte-macrophage progenitors (preGM, Lin-Sca1-cKit+CD41-CD16/32-CD105-CD150-) and granulocyte-macrophage progenitors (GMP, Lin-Sca1-cKit+CD41-CD16/32+CD150-) are expanded in poly I:C treated mice

abnormal megakaryocyte morphology ( J:262170 )

• the megakaryocytes that replace normal hematopoiesis in bone marrow of poly I:C treated mice display nuclear atypia and are accompanied by increased levels of reticulin and atypical megakaryocytes without increased levels of reticulin are seen in the spleen

increased megakaryocyte cell number ( J:262170 )

• poly I:C treated mice show increased numbers of megakaryocytes in bone marrow and spleen

increased erythroid progenitor cell number ( J:262170 )

• pre-CFU-erythroid progenitors (preCFU-E, Lin-Sca1-cKit+CD41-CD16/32-CD105+CD150+) are increased in the spleen of poly I:C treated mice

increased megakaryocyte progenitor cell number ( J:262170 )

• bone marrow and spleen show increased proportion of megakaryocytic progenitors (Lin-Sca1-cKit+CD150+CD41+)

decreased erythroblast number ( J:262170 )

• erythroblasts (CD71+Ter119+) are reduced in bone marrow of poly I:C treated mice

decreased hematocrit ( J:262170 )

• poly I:C treated mice exhibit reduced hematocrit

thrombocytosis ( J:262170 )

• mice develop extreme thrombocytosis by 3 to 4 months after polyinosinic:polycytidylic acid (poly I:C) treatment

• thrombocytosis is transplantable: wild-type recipient mice transplanted with bone marrow cells from homozygous mice after poly I:C develop extreme thrombocytosis

• however, the long-term in vivo repopulating activity of bone marrow cells in competitive bone marrow transplantation is normal

increased leukocyte cell number ( J:262170 )

• modest, but significant, increase in white blood cell numbers in poly I:C treated mice

• leukocytosis is transplantable: wild-type recipient mice transplanted with bone marrow cells from homozygous mice after poly I:C develop leukocytosis

increased hematopoietic stem cell number ( J:262170 )

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

abnormal spleen morphology ( J:262170 )

• spleen from poly I:C treated mice shows destruction of normal splenic architecture with increased numbers of atypical megakaryocytes without increased levels of reticulin

enlarged spleen ( J:262170 )

• by 6-7 months after poly I:C, mice show splenomegaly

immune system

increased leukocyte cell number ( J:262170 )

• modest, but significant, increase in white blood cell numbers in poly I:C treated mice

• leukocytosis is transplantable: wild-type recipient mice transplanted with bone marrow cells from homozygous mice after poly I:C develop leukocytosis

abnormal spleen morphology ( J:262170 )

• spleen from poly I:C treated mice shows destruction of normal splenic architecture with increased numbers of atypical megakaryocytes without increased levels of reticulin

enlarged spleen ( J:262170 )

• by 6-7 months after poly I:C, mice show splenomegaly

growth/size/body

enlarged spleen ( J:262170 )

• by 6-7 months after poly I:C, mice show splenomegaly

skeleton

abnormal bone marrow morphology ( J:262170 )

• bone morrow of poly I:C treated mice shows almost complete effacement of normal hematopoiesis by megakaryocytes that display nuclear atypia and are accompanied by increased levels of reticulin

myelofibrosis ( J:262170 )

• mice treated with poly I:C exhibit myelofibrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
essential thrombocythemia		DOID:2224	OMIM:187950 OMIM:601977 OMIM:614521	J:262170
myelofibrosis		DOID:4971	OMIM:254450	J:262170