Phenotypes Associated with This Genotype

Genotype
MGI:5441332

• Allelic Composition: Tg(Igkv3-5*-MYC)24Plbe/0
• Genetic Background: C57BL/6J-Tg(Igkv3-5*-MYC)DLoxP4Plbe/PlbeMmmh

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:131912 )

• median survival of 594 days in 2 of 8 mice following secondary immunization with NP-CGG

premature death ( J:131912 )

• median survival of 661 days

immune system

abnormal plasma cell differentiation ( J:131912 )

• extramedullary plasma cell expansion

increased plasma cell number ( J:131912 )

• slowly progressive monoclonal expansion exclusively in the bone marrow

abnormal humoral immune response ( J:131912 )

• mice exhibit a spike in monoclonal antibodies (M-spikes) starting at 20 weeks of age that increases with age

• following secondary immunization, 2 of 8 mice immunized with NP-CGG exhibit M-spikes unlike control mice

• however, mice treated with melphalan, dexamethasone, and bortezomib exhibit reduced M-spike levels

abnormal immunoglobulin level ( J:131912 )

• two mice develop type 1 cryoglobulinemia

• serum immunoglobin detected in the tubuli and glomeruli of the kidney

increased IgG1 level ( J:131912 )

• at 70 weeks

increased IgG3 level ( J:131912 )

• at 70 weeks

hematopoietic system

abnormal plasma cell differentiation ( J:131912 )

• extramedullary plasma cell expansion

anemia ( J:131912 )

abnormal hemoglobin ( J:131912 )

• lower median hemoglobin concentration at necropsy

increased plasma cell number ( J:131912 )

• slowly progressive monoclonal expansion exclusively in the bone marrow

abnormal immunoglobulin level ( J:131912 )

• two mice develop type 1 cryoglobulinemia

• serum immunoglobin detected in the tubuli and glomeruli of the kidney

increased IgG1 level ( J:131912 )

• at 70 weeks

increased IgG3 level ( J:131912 )

• at 70 weeks

skeleton

abnormal vertebrae morphology ( J:131912 )

• vertebral collapse occasionally observed

abnormal bone structure ( J:131912 )

• lytic bone lesions occasionally observed

decreased bone mineral density ( J:131912 )

decreased bone trabecula number ( J:131912 )

osteoporosis ( J:131912 )

neoplasm

increased B cell derived lymphoma incidence ( J:131912 )

• 2 of 122 mice develop very aggressive, highly proliferative, isotype class-switched, somatically mutate Burkitt's lymphoma that invade multiple organs and infiltrate the bone marrow, disappearance of M-spikes and reversion of the mutated stop codon

increased myeloma incidence ( J:131912 )

• in aged mice, confined to the bone marrow

increased plasmacytoma incidence ( J:131912 )

• clonally related, proliferative, extramedullary plasmacytoma in some mice that spreads to the spleen, lymph nodes and peritoneal cavity with ascites

• following secondary immunization, 2 of 8 mice immunized with NP-CGG exhibit increased incidence of progression to extramedullary plasmacytoma unlike control mice

behavior/neurological

hindlimb paralysis ( J:131912 )

• occasionally

homeostasis/metabolism

ascites ( J:131912 )

• in some mice with plasmacytoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple myeloma		DOID:9538	OMIM:254500	J:131912