Phenotypes associated with this allele

• Allele Symbol: Tg(Cd4-NPM/ALK)N1Ingh
• Allele Name: transgene insertion N1, Giorgio Inghirami
• Allele ID: MGI:3833917
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Rag2^tm1Fwa/Rag2^tm1Fwa Tg(Cd4-NPM/ALK)N1Ingh/0	involves: 129S/SvEv * C57BL/6 * Swiss Webster	MGI:5811095
cx2	Rag2^tm1Fwa/Rag2^tm1Fwa Tg(Cd4-NPM/ALK)N1Ingh/0 Tg(TcraTcrb)1100Mjb/0	involves: 129S/SvEv * C57BL/6 * Swiss Webster	MGI:5811096
cx3	Tg(Cd4-NPM/ALK)N1Ingh/0 Tg(TcraTcrb)1100Mjb/0	involves: C57BL/6 * Swiss Webster	MGI:5811097
tg4	Tg(Cd4-NPM/ALK)N1Ingh/0	either: (involves: BALB/c * Swiss Webster) or (involves: C57BL/6 * Swiss Webster)	MGI:5805976
tg5	Tg(Cd4-NPM/ALK)N1Ingh/0	involves: C57BL/6 * Swiss Webster	MGI:5811093

Genotype
MGI:5811095

cx1

• Allelic Composition: Rag2^tm1Fwa/Rag2^tm1Fwa; Tg(Cd4-NPM/ALK)N1Ingh/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * Swiss Webster

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

neoplasm

increased thymus tumor incidence ( J:235890 )

• mice develop thymic tumors consisting of cells of the double-positive stage of T-cell development

• development of tumors is delayed compared to single Tg(Cd4-NPM/ALK)N1Ingh transgenic mice

increased T cell derived lymphoma incidence ( J:235890 )

• cortical thymic lymphoma

endocrine/exocrine glands

increased DN3 thymocyte number ( J:235890 )

increased thymus tumor incidence ( J:235890 )

• mice develop thymic tumors consisting of cells of the double-positive stage of T-cell development

• development of tumors is delayed compared to single Tg(Cd4-NPM/ALK)N1Ingh transgenic mice

increased T cell derived lymphoma incidence ( J:235890 )

• cortical thymic lymphoma

hematopoietic system

increased DN3 thymocyte number ( J:235890 )

immune system

increased DN3 thymocyte number ( J:235890 )

Genotype
MGI:5811096

cx2

• Allelic Composition: Rag2^tm1Fwa/Rag2^tm1Fwa; Tg(Cd4-NPM/ALK)N1Ingh/0; Tg(TcraTcrb)1100Mjb/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * Swiss Webster

neoplasm

increased gastrointestinal stromal tumor incidence ( J:235890 )

• mice do not develop lymphoid tumors, but present after a long latency with gastrointestinal stromal tumors

increased hepatocellular carcinoma incidence ( J:235890 )

• mice present after a long latency with hepatocellular carcinomas and sarcomas

increased sarcoma incidence ( J:235890 )

• mice present after a long latency with hepatocellular carcinomas and sarcomas

digestive/alimentary system

increased gastrointestinal stromal tumor incidence ( J:235890 )

• mice do not develop lymphoid tumors, but present after a long latency with gastrointestinal stromal tumors

liver/biliary system

increased hepatocellular carcinoma incidence ( J:235890 )

• mice present after a long latency with hepatocellular carcinomas and sarcomas

Genotype
MGI:5811097

cx3

• Allelic Composition: Tg(Cd4-NPM/ALK)N1Ingh/0; Tg(TcraTcrb)1100Mjb/0
• Genetic Background: involves: C57BL/6 * Swiss Webster

mortality/aging

premature death ( J:235890 )

• means survival of 181 days

neoplasm

increased gastrointestinal stromal tumor incidence ( J:235890 )

• mice exposed to MHV-OVA develop heptoacellular carcinomas and sarcomas

increased T cell derived lymphoma incidence ( J:235890 )

• mice develop ALK+ lymphomas, with a peripheral rather than thymic presentation

• tumors show cells with eosinophilic cytoplasm and reniform nuclei, resembling the classic hallmark cells of human anaplastic large cell lymphoma

• tumors do not show endogenous TCRbeta rearrangements

• mice exposed to MHV-OVA show abrogated anaplastic large cell lymphoma development

increased hepatocellular carcinoma incidence ( J:235890 )

• mice exposed to MHV-OVA show abrogated anaplastic large cell lymphoma development and develop hepatocellular carcinomas and sarcomas

increased sarcoma incidence ( J:235890 )

• mice exposed to MHV-OVA develop heptoacellular carcinomas and sarcomas

digestive/alimentary system

increased gastrointestinal stromal tumor incidence ( J:235890 )

• mice exposed to MHV-OVA develop heptoacellular carcinomas and sarcomas

endocrine/exocrine glands

abnormal thymus morphology ( J:235890 )

• total thymic cellularity is increased

• however, mice have normal T-cell development profiles

increased T cell derived lymphoma incidence ( J:235890 )

• mice develop ALK+ lymphomas, with a peripheral rather than thymic presentation

• tumors show cells with eosinophilic cytoplasm and reniform nuclei, resembling the classic hallmark cells of human anaplastic large cell lymphoma

• tumors do not show endogenous TCRbeta rearrangements

• mice exposed to MHV-OVA show abrogated anaplastic large cell lymphoma development

hematopoietic system

abnormal thymus morphology ( J:235890 )

• total thymic cellularity is increased

• however, mice have normal T-cell development profiles

abnormal double-negative T cell morphology ( J:235890 )

• increase in cellular proliferation of the DN3 population

immune system

abnormal thymus morphology ( J:235890 )

• total thymic cellularity is increased

• however, mice have normal T-cell development profiles

abnormal double-negative T cell morphology ( J:235890 )

• increase in cellular proliferation of the DN3 population

liver/biliary system

increased hepatocellular carcinoma incidence ( J:235890 )

• mice exposed to MHV-OVA show abrogated anaplastic large cell lymphoma development and develop hepatocellular carcinomas and sarcomas

Genotype
MGI:5805976

tg4

• Allelic Composition: Tg(Cd4-NPM/ALK)N1Ingh/0
• Genetic Background: either: (involves: BALB/c * Swiss Webster) or (involves: C57BL/6 * Swiss Webster)

neoplasm

increased plasmacytoma incidence ( J:82127 )

• plasmacytomas occurring in lymph nodes, spleen, and very rarely the thymus often completely replace these lymphoid organs and invade the surrounding tissues

increased hemolymphoid system tumor incidence ( J:82127 )

• 100% of mice develop spontaneous lymphoid tumors beginning at 5 weeks of age

• tumors are mainly thymic lymphomas or plasma cell neoplasms

increased lymphoblastic lymphoma incidence ( J:82127 )

• T cell tumors are exclusively lymphoblastic lymphomas

increased myeloma incidence ( J:82127 )

• greater than 80% prevalence of plasma cell tumors

• plasma cell tumors are of three types: tumors composed primary of mature plasma cells characterized by a large cytoplasm and eccentric and sometimes binucleated nuclei with evident nucleoli, tumors with large atypical cells with irregular nuclei and conscious nucleoli, and tumors with atypical, pleomorphic/anaplastic cells

• in 20% of mice, the neoplastic plasma cells occupy the bone marrow spaces and invade into the vertebral bones

• tumors are of B-cell origin and express clonal immunoglobulin

mortality/aging

premature death ( J:82127 )

• mean survival of 17 weeks

behavior/neurological

hindlimb paralysis ( J:82127 )

• mice that have neoplastic plasma cell invasion into vertebral bones and the central nervous system show frequent gross limb paralysis and other postural and behavioral habits

endocrine/exocrine glands

increased lymphoblastic lymphoma incidence ( J:82127 )

• T cell tumors are exclusively lymphoblastic lymphomas

hematopoietic system

increased immunoglobulin level ( J:82127 )

• serum shows presence of free light chain immunoglobulin

immune system

increased immunoglobulin level ( J:82127 )

• serum shows presence of free light chain immunoglobulin

nervous system

abnormal dorsal root ganglion morphology ( J:82127 )

• neoplastic plasma cells that invade into vertebral bones compress and often destroy the spinal ganglia

abnormal spinal nerve morphology ( J:82127 )

• neoplastic plasma cells that invade into vertebral bones compress and often destroy the spinal nerves

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple myeloma		DOID:9538	OMIM:254500	J:82127

Genotype
MGI:5811093

tg5

• Allelic Composition: Tg(Cd4-NPM/ALK)N1Ingh/0
• Genetic Background: involves: C57BL/6 * Swiss Webster

mortality/aging

premature death ( J:235890 )

• mean survival of 88 days

neoplasm

increased thymus tumor incidence ( J:235890 )

• mice develop thymic tumors

endocrine/exocrine glands

increased DN3 thymocyte number ( J:235890 )

• accumulation of phenotypic DN3 cells at 5 weeks of age

increased thymus tumor incidence ( J:235890 )

• mice develop thymic tumors

hematopoietic system

abnormal T cell morphology ( J:235890 )

• increase in CD44^hi population of thymocytes

abnormal T cell differentiation ( J:235890 )

• accumulation of phenotypic DN3 cells at 5 weeks of age and an increase in the percentage of the total thymic population expressing CD117, indicating a delay in T-cell development at the DN3 stage

increased DN3 thymocyte number ( J:235890 )

• accumulation of phenotypic DN3 cells at 5 weeks of age

immune system

abnormal T cell morphology ( J:235890 )

• increase in CD44^hi population of thymocytes

abnormal T cell differentiation ( J:235890 )

• accumulation of phenotypic DN3 cells at 5 weeks of age and an increase in the percentage of the total thymic population expressing CD117, indicating a delay in T-cell development at the DN3 stage

increased DN3 thymocyte number ( J:235890 )

• accumulation of phenotypic DN3 cells at 5 weeks of age