Phenotypes associated with this allele

• Allele Symbol: Jak2^{tm1(JAK2)Argr}
• Allele Name: targeted mutation 1, Anthony R Green
• Allele ID: MGI:4836590
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Jak2^tm1(JAK2)Argr/Jak2^+ Dppa3^tm1(cre)Peli/Dppa3^+	involves: 129S5/SvEvBrd * 129S7/SvEvBrd * C57BL/6	MGI:6784096
cn2	Jak2^tm1(JAK2)Argr/Jak2^+ Tg(Mx1-cre)1Cgn/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:4836619

Genotype
MGI:6784096

cn1

• Allelic Composition: Jak2^{tm1(JAK2)Argr}/Jak2⁺; Dppa3^tm1(cre)Peli/Dppa3⁺
• Genetic Background: involves: 129S5/SvEvBrd * 129S7/SvEvBrd * C57BL/6

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

growth/size/body

increased spleen weight ( J:233169 )

• untreated mice show significantly increased mean spleen weight

• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 2 months restores spleen weight to wild-type levels

hematopoietic system

increased spleen weight ( J:233169 )

• untreated mice show significantly increased mean spleen weight

• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 2 months restores spleen weight to wild-type levels

thrombocytosis ( J:233169 )

• untreated mice show increased platelet number in peripheral blood

• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 1 or 2 months leads to a significant reduction in peripheral platelet number

increased leukocyte cell number ( J:233169 )

• untreated mice show increased leukocyte number in peripheral blood

• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 1 or 2 months leads to a significant reduction in peripheral leukocyte number

increased hematopoietic stem cell number ( J:233169 )

• untreated mice show significantly increased % and absolute number of LSK+ cells in the bone marrow

• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 2 months restores % and absolute number of LSK+ cells in the bone marrow to wild-type levels

neoplasm

increased chronic myelocytic leukemia incidence ( J:233169 )

• mice develop myeloproliferative neoplasm (MPN)-associated hematologic phenotypes

• daily treatment with IGF1R kinase inhibitor NVP-AEW541 ameliorates MPN-related phenotypes

homeostasis/metabolism

abnormal protein level ( J:233169 )

• mice exhibit a 50% reduction in ZFAND2B protein levels and a 2.2-fold increase in IGF1R (insulin-like growth factor I receptor) protein levels relative to wild-type controls

• Zfand2b mRNA levels are reduced in the bone marrow

immune system

increased spleen weight ( J:233169 )

• untreated mice show significantly increased mean spleen weight

• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 2 months restores spleen weight to wild-type levels

increased leukocyte cell number ( J:233169 )

• untreated mice show increased leukocyte number in peripheral blood

• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 1 or 2 months leads to a significant reduction in peripheral leukocyte number

Genotype
MGI:4836619

cn2

• Allelic Composition: Jak2^{tm1(JAK2)Argr}/Jak2⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

growth/size/body

enlarged spleen ( J:164539 )

• in 10% of mice following pIpC administration

hematopoietic system

enlarged spleen ( J:164539 )

• in 10% of mice following pIpC administration

abnormal erythropoiesis ( J:164539 )

• at 6 and 26 weeks following pIpC administration, the number of pro-erythrocytes and terminally differentiated erythroblasts is increased compared to in wild-type mice

anemia ( J:164539 )

• in one mouse following pIpC administration

abnormal bone marrow cell morphology/development ( J:164539 )

• following pIpC administration,10% of mice exhibit increase in Ter119+ erythroid cells in bone marrow (BM), CD71+Ter119+ erythroid cells in the spleen, and Mac1+Gr1+ cells in BM and spleen compared with wild-type mice

• following pIpC administration, one mouse exhibited granulocytic hyperplasia, patchy accumulation of immature cells, reduction of erythroid and megakaryocytic cells, development of collagen fibrosis, decreased Ter119+ erythroid cells in BM, increased CD71+Ter119+ erythroid cells in the spleen, and increased Mac1+Gr1+ cells in BM and spleen compared with wild-type mice

abnormal megakaryocyte differentiation ( J:164539 )

• 26 weeks following pIpC administration, the number of Gr+Mac1+ cells is modestly increased compared to in wild-type mice

• 10 weeks after pIpC treatment, bone marrow cells exposed to thrombopoietin (TPO) exhibit increased number of ploidy CD41+ cells compared with similarly treated wild-type cells

abnormal common myeloid progenitor cell morphology ( J:164539 )

• 6 weeks, but not 26 weeks, after pIpC treatment, mice exhibit increased bone marrow-derived colony-forming units-granulocyte, colony-forming units-macrophage, and colony forming units granulocyte-macrophage (CFU-GM) compared with wild-type mice

• however, no TPO-independent megakaryocyte colonies are observed

increased megakaryocyte cell number ( J:164539 )

• at 6 and 26 weeks following pIpC administration, mice exhibit megakaryocytic hyperplasia with large and hyperlobated forms unlike in wild-type mice

increased erythroid progenitor cell number ( J:164539 )

• modestly at 6 weeks after pIpC treatment in the presence or absence of erythropoietin (EPO)

• significant at 26 weeks after pIpC and EPO treatment with an increase in EPO-independent BFU-E at 26 weeks

increased erythrocyte cell number ( J:164539 )

• in 10% of mice following pIpC administration

increased hematocrit ( J:164539 )

• in 10% of mice following pIpC administration

increased hemoglobin content ( J:164539 )

• following pIpC administration

thrombocytosis ( J:164539 )

• following pIpC administration

decreased leukocyte cell number ( J:164539 )

• in one mouse following pIpC administration

increased leukocyte cell number ( J:164539 )

• following pIpC administration

decreased hematopoietic stem cell number ( J:164539 )

• after pIpC treatment, mice exhibit reduced numbers of LSK cells compared with wild-type mice

abnormal hematopoietic system physiology ( J:164539 )

• after pIpC treatment, LSK cells exhibit increased DNA damage, reduced cell cycling, and reduced apoptosis compared with wild-type mice

• in transplantation assays, hematopoietic stem cells from pIpC treated mice exhibits impaired long-term repopulation compared with wild-type cells

immune system

enlarged spleen ( J:164539 )

• in 10% of mice following pIpC administration

decreased leukocyte cell number ( J:164539 )

• in one mouse following pIpC administration

increased leukocyte cell number ( J:164539 )

• following pIpC administration

skeleton

myelofibrosis ( J:164539 )

• following pIpC administration,10% of mice exhibit bone marrow fibrosis unlike wild-type mice

cellular

abnormal megakaryocyte differentiation ( J:164539 )

• 26 weeks following pIpC administration, the number of Gr+Mac1+ cells is modestly increased compared to in wild-type mice

• 10 weeks after pIpC treatment, bone marrow cells exposed to thrombopoietin (TPO) exhibit increased number of ploidy CD41+ cells compared with similarly treated wild-type cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
essential thrombocythemia		DOID:2224	OMIM:187950 OMIM:601977 OMIM:614521	J:164539