Phenotypes associated with this allele

• Allele Symbol: Pml^tm1Ppp
• Allele Name: targeted mutation 1, Pier P Pandolfi
• Allele ID: MGI:2429949
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pml^tm1Ppp/Pml^tm1Ppp	FVB.129S7-Pml^tm1Ppp	MGI:6195075
hm2	Pml^tm1Ppp/Pml^tm1Ppp	involves: 129S7/SvEvBrd	MGI:3041145
cx3	Pml^tm1Ppp/Pml^+ Trp53^tm3.1Glo/Trp53^tm3.1Glo	B6.129S7(Cg)-Pml^tm1Ppp Trp53^tm3.1Glo	MGI:7485800
cx4	Pml^tm1Ppp/Pml^tm1Ppp Trp53^tm3.1Glo/Trp53^tm3.1Glo	B6.129S7(Cg)-Pml^tm1Ppp Trp53^tm3.1Glo	MGI:7485803
cx5	Pml^tm1Ppp/Pml^+ Trp53^tm3.1Glo/Trp53^+	B6.129S7(Cg)-Pml^tm1Ppp Trp53^tm3.1Glo	MGI:7485831
cx6	Pml^tm1Ppp/Pml^tm1Ppp Trp53^tm3.1Glo/Trp53^+	B6.129S7(Cg)-Pml^tm1Ppp Trp53^tm3.1Glo	MGI:7485838

Genotype
MGI:6195075

hm1

• Allelic Composition: Pml^tm1Ppp/Pml^tm1Ppp
• Genetic Background: FVB.129S7-Pml^tm1Ppp

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

cellular

abnormal double-strand DNA break repair ( J:262172 )

• primary MEFs do not exhibit a defect in nonhomologous end-joining (NHEJ) but show a reduction in the efficiency of the homologous recombination pathway

hematopoietic system

increased hematopoietic stem cell number ( J:262172 )

• the number of LSK hematopoietic stem and progenitor cells is increased

• acceleration of cell cycle progression in LSK hematopoietic stem cells

homeostasis/metabolism

abnormal double-strand DNA break repair ( J:262172 )

• primary MEFs do not exhibit a defect in nonhomologous end-joining (NHEJ) but show a reduction in the efficiency of the homologous recombination pathway

Genotype
MGI:3041145

hm2

• Allelic Composition: Pml^tm1Ppp/Pml^tm1Ppp
• Genetic Background: involves: 129S7/SvEvBrd

neoplasm

increased tumor incidence ( J:46381 )

• although there was no increase in spontaneous tumors, possibly due to the very high susceptibility to infection, levels of induced tumors were higher

increased lymphoma incidence ( J:46381 )

• about 50% of induced tumors are T and B cell lymphomas

cellular

abnormal cell physiology ( J:46381 )

increased fibroblast proliferation ( J:46381 )

• increased proliferation of embryo fibroblasts in culture

• S phase population of cells is increased while G₀/G₁ population is decreased

hematopoietic system

abnormal myelopoiesis ( J:46381 )

• overall reduction of circulating myelocytes

• also reduced in spleen, lymph nodes, thymus and bone marrow

decreased leukocyte cell number ( J:46381 )

decreased granulocyte number ( J:46381 )

• marked reduction of circulating granulocytes

immune system

abnormal immune system cell morphology ( J:46381 )

abnormal myelopoiesis ( J:46381 )

• overall reduction of circulating myelocytes

• also reduced in spleen, lymph nodes, thymus and bone marrow

decreased leukocyte cell number ( J:46381 )

decreased granulocyte number ( J:46381 )

• marked reduction of circulating granulocytes

increased susceptibility to bacterial infection ( J:46381 )

• extreme susceptibility to botryomycotic infections

Genotype
MGI:7485800

cx3

• Allelic Composition: Pml^tm1Ppp/Pml⁺; Trp53^tm3.1Glo/Trp53^tm3.1Glo
• Genetic Background: B6.129S7(Cg)-Pml^tm1Ppp Trp53^tm3.1Glo

mortality/aging

premature death ( J:317504 )

♂ • mean survival of male mice is 150 days, i.e., not significantly different from that in males homozygous for Trp53^tm3.1Glo alone (164.5 days)

prenatal lethality, incomplete penetrance ( J:317504 )

♀ • only 12% of females are born, indicating a severe reduction in female survival

Genotype
MGI:7485803

cx4

• Allelic Composition: Pml^tm1Ppp/Pml^tm1Ppp; Trp53^tm3.1Glo/Trp53^tm3.1Glo
• Genetic Background: B6.129S7(Cg)-Pml^tm1Ppp Trp53^tm3.1Glo

mortality/aging

premature death ( J:317504 )

♂ • mean survival of male mice is 156.5 days i.e., not significantly different from that in males homozygous for Trp53^tm3.1Glo alone (164.5 days)

prenatal lethality, incomplete penetrance ( J:317504 )

♀ • only 9% of females are born, indicating a severe reduction in female survival

Genotype
MGI:7485831

cx5

• Allelic Composition: Pml^tm1Ppp/Pml⁺; Trp53^tm3.1Glo/Trp53⁺
• Genetic Background: B6.129S7(Cg)-Pml^tm1Ppp Trp53^tm3.1Glo

mortality/aging

premature death ( J:317504 )

• median survival for the combined population of both males and females is 504 days, i.e., similar to that of mice heterozygous for Trp53 ^tm3.1Glo alone (499 days)

• median survival is 539 days for male mice and 488 days for female mice, indicating that loss of a single Pml allele does not reduce the mean survival of either male or female Trp53 ^tm3.1Glo heterozygotes

decreased tumor-free survival time ( J:317504 )

♂ • average survival of male mice that present with soft tissue sarcomas (42%) is 443 days

neoplasm

increased lymphoma incidence ( J:317504 )

• 43% of mice develop lymphomas (when expressed as a % of tumor type); 14% of mice develop two tumor types, lymphomas and sarcomas

• 38% of mice exhibit lymphomas when tumor incidence is evaluated per mouse, including those that succumb to EMH, and expressed as a % disease/total number of mice

• when tumors are segregated by gender, 33% of males and 42% of females exhibit lymphomas (expressed as a % disease/total number of mice)

increased T cell derived lymphoma incidence ( J:317504 )

• ~20% of lymphoid tumors are T-cell lymphomas

increased B cell derived lymphoma incidence ( J:317504 )

• immunophenotyping of lymphocytes from terminally resected tumors showed that ~80% of lymphoid tumors are B-cell lymphomas

increased carcinoma incidence ( J:317504 , J:317504 )

• 5% of mice develop carcinomas (when expressed as a % of tumor type) (J:317504)

• 4% of mice exhibit carcinomas (when expressed as a % disease/total number of mice) (J:317504)

♀ • when tumors are segregated by gender, 0% of males and 8% of females exhibit carcinomas (expressed as a % disease/total number of mice) (J:317504)

increased sarcoma incidence ( J:317504 )

• 52% of mice develop sarcomas (when expressed as a % of tumor type); 14% of mice develop two tumor types, lymphomas and sarcomas

• 46% of mice exhibit sarcomas (when expressed as a % disease/total number of mice)

• when tumors are segregated by gender, 42% of males and 17% of females exhibit soft-tissue sarcomas (expressed as a % disease/total number of mice)

increased osteosarcoma incidence ( J:317504 )

• when tumors are segregated by gender, 8% of males and 25% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)

hematopoietic system

increased T cell derived lymphoma incidence ( J:317504 )

• ~20% of lymphoid tumors are T-cell lymphomas

hepatosplenomegaly ( J:317504 )

• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 ^tm3.1Glo alone

extramedullary hematopoiesis ( J:317504 )

• 33% mice exhibit extramedullary hematopoiesis (EMH)

• when segregated by gender, 33% of males and 33% of females exhibit EMH

immune system

increased T cell derived lymphoma incidence ( J:317504 )

• ~20% of lymphoid tumors are T-cell lymphomas

hepatosplenomegaly ( J:317504 )

• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 ^tm3.1Glo alone

liver/biliary system

hepatosplenomegaly ( J:317504 )

• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 ^tm3.1Glo alone

growth/size/body

decreased body weight ( J:317504 )

• average body weight is significantly lower than that in C57BL/6 wild-type controls

hepatosplenomegaly ( J:317504 )

• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 ^tm3.1Glo alone

skeleton

increased osteosarcoma incidence ( J:317504 )

• when tumors are segregated by gender, 8% of males and 25% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:317504 )

• ~20% of lymphoid tumors are T-cell lymphomas

Genotype
MGI:7485838

cx6

• Allelic Composition: Pml^tm1Ppp/Pml^tm1Ppp; Trp53^tm3.1Glo/Trp53⁺
• Genetic Background: B6.129S7(Cg)-Pml^tm1Ppp Trp53^tm3.1Glo

mortality/aging

decreased tumor-free survival time ( J:317504 , J:317504 )

• median survival for the combined population of both males and females is 448 days, i.e., ~50 days shorter than in mice heterozygous for Trp53 ^tm3.1Glo alone (499 days) and in mice heterozygous for both Trp53 ^tm3.1Glo and Pml^tm1Ppp (504 days) (J:317504)

♂ • strikingly, median survival is 414 days for male mice, i.e., >100 days shorter than in males heterozygous for Trp53 ^tm3.1Glo alone (515 days) and in males heterozygous for both Trp53 ^tm3.1Glo and Pml^tm1Ppp (539 days) (J:317504)

♂ • average survival of male mice with soft tissue sarcomas (44%) is 380 days, i.e., even shorter than in males heterozygous for both Trp53 ^tm3.1Glo and Pml^tm1Ppp (443 days) which develop soft tissue sarcomas with a similar frequency (42%) (J:317504)

♂ • however, median survival for female mice is 485 days, i.e., not significantly different from that in males heterozygous for Trp53 ^tm3.1Glo alone (515 days) (J:317504)

neoplasm

increased lymphoma incidence ( J:317504 )

• 36% of mice develop lymphomas (when expressed as a % of tumor type); 18% of mice develop two tumor types, lymphomas and sarcomas

• 44% of mice exhibit lymphomas when tumor incidence is evaluated per mouse and expressed as a % disease/total number of mice

• when tumors are segregated by gender, 44% of males and 44% of females exhibit lymphomas (expressed as a % disease/total number of mice)

increased T cell derived lymphoma incidence ( J:317504 )

• ~40% of lymphoid tumors are T-cell lymphomas

increased B cell derived lymphoma incidence ( J:317504 )

• immunophenotyping of lymphocytes from terminally resected tumors showed that ~60% of lymphoid tumors are B-cell lymphomas

increased carcinoma incidence ( J:317504 , J:317504 )

• 5% of mice develop carcinomas (when expressed as a % of tumor type) (J:317504)

• 6% of mice exhibit carcinomas (when expressed as a % disease/total number of mice) (J:317504)

♀ • when tumors are segregated by gender, 0% of males and 11% of females exhibit carcinomas (expressed as a % disease/total number of mice) (J:317504)

increased sarcoma incidence ( J:317504 )

• 59% of mice develop sarcomas (when expressed as a % of tumor type); 18% of mice develop two tumor types, lymphomas and sarcomas

• 72% of mice exhibit sarcomas (when expressed as a % disease/total number of mice)

• when tumors are segregated by gender, 44% of males and 11% of females exhibit soft-tissue sarcomas (expressed as a % disease/total number of mice), indicating that males lacking PML succumb to aggressive soft tissue sarcomas more frequently than females

increased osteosarcoma incidence ( J:317504 )

• when tumors are segregated by gender, 33% of males and 56% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)

• although osteosarcomas are proportionately more abundant in female mice, survival latency is not significantly altered

immune system

increased T cell derived lymphoma incidence ( J:317504 )

• ~40% of lymphoid tumors are T-cell lymphomas

hepatosplenomegaly ( J:317504 )

• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 ^tm3.1Glo alone

liver/biliary system

hepatosplenomegaly ( J:317504 )

• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 ^tm3.1Glo alone

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:317504 )

• ~40% of lymphoid tumors are T-cell lymphomas

skeleton

increased osteosarcoma incidence ( J:317504 )

• when tumors are segregated by gender, 33% of males and 56% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)

• although osteosarcomas are proportionately more abundant in female mice, survival latency is not significantly altered

hematopoietic system

hematopoietic system phenotype ( J:317504 )

N • zero of 18 mice (0%) exhibit extramedullary hematopoiesis (EMH)

N • when segregated by gender, neither male nor female mice exhibit EMH

increased T cell derived lymphoma incidence ( J:317504 )

• ~40% of lymphoid tumors are T-cell lymphomas

hepatosplenomegaly ( J:317504 )

• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 ^tm3.1Glo alone

growth/size/body

growth/size/body region phenotype ( J:317504 )

N • average body weight is not significantly different from that in C57BL/6 wild-type controls

hepatosplenomegaly ( J:317504 )

• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 ^tm3.1Glo alone