Phenotypes associated with this allele

• Allele Symbol: Igha^tm1(Myc)Janz
• Allele Name: targeted mutation 1, Siegfried Janz
• Allele ID: MGI:3046399
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Igha^tm1(Myc)Janz/Igha^+	involves: 129S1/Sv * C57BL/6	MGI:3046402
cx2	Igha^tm1(Myc)Janz/Igha^+ Tg(Tnfsf13b)1Fma/0	involves: 129S1/Sv * C57BL/6 * DBA/2J	MGI:4840220
cx3	Igha^tm1(Myc)Janz/Igha^+ Tg(Igk-V21-Bax)1967Bvn/0	involves: 129S1/Sv * C57BL/6 * FVB/N	MGI:3046405

Genotype
MGI:3046402

ht1

• Allelic Composition: Igha^tm1(Myc)Janz/Igha⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

neoplasm

increased B cell derived lymphoma incidence ( J:90901 )

• transgenic mice display an increased incidence (9.3%) of B cell derived lymphomas with a mean onset of 330 days

hematopoietic system

increased B cell apoptosis ( J:90901 )

• B cell apoptosis is increased about 4.5 fold compared to normal B cells

increased B cell proliferation ( J:90901 )

• B cells proliferate about 2.5 - 3 times faster compared to normal mice

increased plasma cell number ( J:90901 )

• B220^hiCD138⁺, putative plasmablasts, numbers are increased in the bone marrow of transgenic mice

immune system

increased B cell apoptosis ( J:90901 )

• B cell apoptosis is increased about 4.5 fold compared to normal B cells

increased B cell proliferation ( J:90901 )

• B cells proliferate about 2.5 - 3 times faster compared to normal mice

increased plasma cell number ( J:90901 )

• B220^hiCD138⁺, putative plasmablasts, numbers are increased in the bone marrow of transgenic mice

cellular

increased B cell apoptosis ( J:90901 )

• B cell apoptosis is increased about 4.5 fold compared to normal B cells

increased B cell proliferation ( J:90901 )

• B cells proliferate about 2.5 - 3 times faster compared to normal mice

Genotype
MGI:4840220

cx2

• Allelic Composition: Igha^tm1(Myc)Janz/Igha⁺; Tg(Tnfsf13b)1Fma/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA/2J

mortality/aging

premature death ( J:166158 )

• median lifespan of mice with leukemia is 10 months

hematopoietic system

enlarged spleen ( J:166158 )

• splenomegaly is obvious in males after 4 months of age

increased lymphocyte cell number ( J:166158 )

• males develop lymphocytosis at 3 months of age

increased B cell number ( J:166158 )

• males exhibit an increase in blood B-cell number, with an expansion of the CD5+CD3-B220^low IgM^low B-cell population in blood and spleens

increased mature B cell number ( J:166158 )

• B-cell increase results from a monoclonal expansion of mature B cell-like cells

increased spleen white pulp amount ( J:166158 )

• 8 month old spleens of males exhibit enlarged white pulp with loss of normal splenic architecture resulting from a diffuse infiltration of mature lymphocytes

immune system

enlarged spleen ( J:166158 )

• splenomegaly is obvious in males after 4 months of age

increased lymphocyte cell number ( J:166158 )

• males develop lymphocytosis at 3 months of age

increased B cell number ( J:166158 )

• males exhibit an increase in blood B-cell number, with an expansion of the CD5+CD3-B220^low IgM^low B-cell population in blood and spleens

increased mature B cell number ( J:166158 )

• B-cell increase results from a monoclonal expansion of mature B cell-like cells

increased spleen white pulp amount ( J:166158 )

• 8 month old spleens of males exhibit enlarged white pulp with loss of normal splenic architecture resulting from a diffuse infiltration of mature lymphocytes

neoplasm

increased chronic lymphocytic leukemia incidence ( J:166158 )

• mutants, mainly males, develop a CD5+ B-cell lymphoproliferative disease by 8 months of age that resembles human chronic lymphocytic leukemia

• male mice exhibit increased splenic ¹⁸F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) uptake suggesting elevated leukemic cell metabolism

growth/size/body

enlarged spleen ( J:166158 )

• splenomegaly is obvious in males after 4 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic lymphocytic leukemia		DOID:1040	OMIM:109543 OMIM:151400 OMIM:609630 OMIM:612557 OMIM:612558 OMIM:612559	J:166158

Genotype
MGI:3046405

cx3

• Allelic Composition: Igha^tm1(Myc)Janz/Igha⁺; Tg(Igk-V21-Bax)1967Bvn/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * FVB/N

growth/size/body

enlarged spleen ( J:90901 )

• 8 week old double transgenic exhibit splenomegaly with massive accumulation of plasma cells in extrafollicular areas

mortality/aging

decreased tumor-free survival time ( J:90901 )

• survival of double transgenics is markedly decreased as a result of malignant plasma cell tumors

neoplasm

increased leukemia incidence ( J:90901 )

• in some cases plasma cell leukemia is seen

increased plasmacytoma incidence ( J:90901 )

• malignant plasma cell tumors develop rapidly with a mean onset of 135 days, are fully penetrant, proliferate vigorously, occur in multiple tissues including the spleen, bone marrow, and lymph nodes, and may have monocentric or multicentric origins

• bone sections from double transgenic mice with less advanced tumors show multifocal lesions of aberrant pleomorphic plasma cells next to diminished of dissolved osseous trabeculae

• pathalogical fractures of the long bones are seen in some double transgenic mice

hematopoietic system

abnormal B cell apoptosis ( J:90901 )

• B cell apoptosis is increased compared to normal B cells but decreased compared to B cells from Igh-2^tm1Janz single transgenics

enlarged spleen ( J:90901 )

• 8 week old double transgenic exhibit splenomegaly with massive accumulation of plasma cells in extrafollicular areas

abnormal plasma cell morphology ( J:90901 )

• plasma cells participate in cell cycling unlike in normal mice

increased plasma cell number ( J:90901 )

• the bone marrow and spleen contain on average 42% and 34% plasma cells, respectively, compared to less than 2% in normal mice

increased IgG level ( J:90901 )

• elevation of IgG accompanied the increase in plasma cell numbers

increased IgM level ( J:90901 )

• elevation of IgM accompanied the increase in plasma cell numbers

immune system

abnormal B cell apoptosis ( J:90901 )

• B cell apoptosis is increased compared to normal B cells but decreased compared to B cells from Igh-2^tm1Janz single transgenics

enlarged spleen ( J:90901 )

• 8 week old double transgenic exhibit splenomegaly with massive accumulation of plasma cells in extrafollicular areas

abnormal plasma cell morphology ( J:90901 )

• plasma cells participate in cell cycling unlike in normal mice

increased plasma cell number ( J:90901 )

• the bone marrow and spleen contain on average 42% and 34% plasma cells, respectively, compared to less than 2% in normal mice

increased IgG level ( J:90901 )

• elevation of IgG accompanied the increase in plasma cell numbers

increased IgM level ( J:90901 )

• elevation of IgM accompanied the increase in plasma cell numbers

cellular

abnormal B cell apoptosis ( J:90901 )

• B cell apoptosis is increased compared to normal B cells but decreased compared to B cells from Igh-2^tm1Janz single transgenics