Phenotypes associated with this allele

• Allele Symbol: Gt(ROSA)26Sor^{tm4(CAG-hsb5)Nki}
• Allele Name: targeted mutation 4, The Netherlands Cancer Institute
• Allele ID: MGI:4410291
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm4(CAG-hsb5)Nki/Gt(ROSA)26Sor^+ Npm1^tm1Gsva/Npm1^+ TgTn(pb-sb-GrOnc)#aGsva/0 Tg(Mx1-cre)1Cgn/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5007701
cn2	Gt(ROSA)26Sor^tm4(CAG-hsb5)Nki/Gt(ROSA)26Sor^+ Tg(Mx1-cre)1Cgn/0 Tg(Tal1-tTA)19Dgt/0 Tg(tetO-BCR/ABL1)2Dgt/0 TgTn(pb-sb-GrOnc)#aGsva/0	involves: 129P2/OlaHsd * C57BL/6 * CBA/J * DBA/2 * FVB/N	MGI:5806781
cn3	Gt(ROSA)26Sor^tm4(CAG-hsb5)Nki/Gt(ROSA)26Sor^+ Tg(Mx1-cre)1Cgn/0 Tg(tetO-BCR/ABL1)2Dgt/0 TgTn(pb-sb-GrOnc)#aGsva/0	involves: 129P2/OlaHsd * C57BL/6 * CBA/J * FVB/N	MGI:5806786

Genotype
MGI:5007701

cn1

• Allelic Composition: Gt(ROSA)26Sor^{tm4(CAG-hsb5)Nki}/Gt(ROSA)26Sor⁺; Npm1^tm1Gsva/Npm1⁺; TgTn(pb-sb-GrOnc)#aGsva/0; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

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

mortality/aging

premature death ( J:172071 )

• mean survival of pIpC-treated mice is 99 days compared with 150 days for Gt(Rosa)26Sor^{tm4(CAG-hsb5)Nki} Gt(Rosa)26Sor⁺ Tg(Mx1-cre)1Cgn TgTn(pb-sb-GrOnc)#aGsva control mice

neoplasm

increased leukemia incidence ( J:172071 )

• all mice develop aggressive leukemia and/or lymphoma within a year of pIpC induction

increased acute promyelocytic leukemia incidence ( J:172071 )

• in pIpC-treated mice

increased lymphoma incidence ( J:172071 )

• all mice develop aggressive leukemia and/or lymphoma within a year of pIpC induction

• however, pIpC-treated mice do not develop T cell lymphomas unlike in control mice

increased B cell derived lymphoma incidence ( J:172071 )

• in some pIpC-treated mice

increased hemangiosarcoma incidence ( J:172071 )

• angiosarcoma in some pIpC-treated mice

Genotype
MGI:5806781

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm4(CAG-hsb5)Nki}/Gt(ROSA)26Sor⁺; Tg(Mx1-cre)1Cgn/0; Tg(Tal1-tTA)19Dgt/0; Tg(tetO-BCR/ABL1)2Dgt/0; TgTn(pb-sb-GrOnc)#aGsva/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA/J * DBA/2 * FVB/N

mortality/aging

premature death ( J:227558 )

• mice withdrawn from tetracycline and treated with polyinosine-polycyticylic acid (pIpC) show a decrease in survival with median survival of 116.5 days

neoplasm

increased chronic myelocytic leukemia incidence ( J:227558 )

• majority of pIpC treated mice (85%) develop an exclusively myeloid and primary acute leukemia phenotype

• 5% of mice remain in the chronic phase of the disease

• about 10% of mice develop an accelerated phase-like phenotype but with less than 20% blasts

• however, mice do not develop lymphoid leukemias

hematopoietic system

increased spleen weight ( J:227558 )

• in pIpC treated mice

decreased hemoglobin content ( J:227558 )

• hemoglobin levels are decreased in pIpC treated mice

increased leukocyte cell number ( J:227558 )

• upon withdrawal of tetracycline and treatment with pIpC, mice develop moderate, but persistent (2-3 fold) increase of white blood counts

• white blood cell counts at the terminal endpoint are elevated, indicating a dramatic preterminal proliferative change in kinetics of their disease

increased granulocyte number ( J:227558 )

• upon withdrawal of tetracycline and treatment with pIpC, mice show marked expansion of the granulocyte compartment

• increase in infiltration of tissues with both granulocytes and immature cells

increased basophil cell number ( J:227558 )

• disease progression in in pIpC treated mice is frequently accompanied by an increase in basophils

increased myeloid cell number ( J:227558 )

• the myeloid progenitor compartment is expanded in pIpC treated mice, including the granulocyte monocyte progenitor compartment

increased hematopoietic stem cell number ( J:227558 )

• expansion of the lineage-negative (Lin-) bone marrow fraction in pIpC treated mice

• however, no differences are seen in total Lin-Sca+c-kit+ (LSK) numbers, long-term and short-term hematopoietic stem cell or multipotent progenitor proportions

abnormal hematopoietic stem cell physiology ( J:227558 )

• hematopoietic stem cells show an increased ability to serially replate compared to control cells

immune system

increased spleen weight ( J:227558 )

• in pIpC treated mice

increased leukocyte cell number ( J:227558 )

• upon withdrawal of tetracycline and treatment with pIpC, mice develop moderate, but persistent (2-3 fold) increase of white blood counts

• white blood cell counts at the terminal endpoint are elevated, indicating a dramatic preterminal proliferative change in kinetics of their disease

increased granulocyte number ( J:227558 )

• upon withdrawal of tetracycline and treatment with pIpC, mice show marked expansion of the granulocyte compartment

• increase in infiltration of tissues with both granulocytes and immature cells

increased basophil cell number ( J:227558 )

• disease progression in in pIpC treated mice is frequently accompanied by an increase in basophils

liver/biliary system

increased liver weight ( J:227558 )

• in pIpC treated mice

growth/size/body

increased liver weight ( J:227558 )

• in pIpC treated mice

increased spleen weight ( J:227558 )

• in pIpC treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:227558

Genotype
MGI:5806786

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm4(CAG-hsb5)Nki}/Gt(ROSA)26Sor⁺; Tg(Mx1-cre)1Cgn/0; Tg(tetO-BCR/ABL1)2Dgt/0; TgTn(pb-sb-GrOnc)#aGsva/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA/J * FVB/N

mortality/aging

premature death ( J:227558 )

• mice withdrawn from tetracycline and treated with polyinosine-polycyticylic acid (pIpC) show a median survival of 125.5 days

neoplasm

increased leukemia incidence ( J:227558 )

• 26% of mice treated with pIpC develop lymphoid acute leukemias

• 70% of mice treated with pIpC develop myeloid acute leukemias

• increase in infiltration of tissues with immature cells