Phenotypes Associated with This Genotype

Genotype
MGI:5301598

• Allelic Composition: Tg(H2-L-IL6)46Kish/Tg(H2-L-IL6)46Kish
• Genetic Background: C.B6-Tg(H2-L-IL6)46Kish

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

mortality/aging

premature death ( J:74377 , J:177820 )

• almost all mutants die by 18 months of age (J:74377)

• some mutants die with renal disease (J:74377)

• while many mutants die around 8 to 9 months of age from severe systemic AA amyloidosis, some mutants develop amyloidosis by 3-5 months of age and die sooner (J:177820)

neoplasm

increased B cell derived lymphoma incidence ( J:74377 )

• 29% of mutants develop B cell lymphomas

• mutants with B cell lymphoma include cases of follicular B cell lymphoma and diffuse large-cell B cell lymphoma

increased follicular lymphoma incidence ( J:74377 )

increased plasmacytoma incidence ( J:74377 )

• mutants begin to develop plasmacytoma at 6 months of age such that 56% of mutants have plasmacytoma in the lymph nodes, Peyer's patches and/or spleen by 18 months of age

• mice that develop B cell lymphomas also develop plasmacytoma, often in the form of multicentric microplasmacytoma

• 16% of mutants remain tumor free but are at the transitional stage between plasma cell hyperplasia, multicentric microplasmacytoma and plasmacytoma

• tumors are of three subtypes, either a typical mature plasmacytic form, a less mature plasmacytoid or plasmablastic form, or highly aggressive anaplastic form

• mice with anaplastic or plasmablastic plasmacytoma do not exhibit M-components in the serum

• plasmacytomas and some lymphomas are characterized by Myc-activating T(12;15) chromosomal translocations, but do not express IgA

immune system

abnormal spleen trabecular artery morphology ( J:177820 )

• amyloid deposits cause irregular thickening of the arterial walls within the splenic trabeculae

enlarged spleen ( J:177820 )

• due to amyloid deposits and probably also follicular lymphoid hyperplasia and plasmacytosis

• amyloid deposits distort the normal splenic architecture, separating the trabeculae and periarteriolar lymphoid sheaths and expanding the extracellular matrix of the reticular fiber network of the sinusoids

abnormal spleen trabecular vein morphology ( J:177820 )

• amyloid deposits cause irregular thickening of the venous walls within the splenic trabeculae

increased IgG level ( J:74377 )

• mutants without lymphoid neoplasia exhibit an increase in serum polyclonal Ig levels, specifically IgG1 and IgG2b, and the presence of M-components

increased IgG1 level ( J:74377 )

increased IgG2b level ( J:74377 )

behavior/neurological

poor grooming ( J:177820 )

• fail to groom adequately

hunched posture ( J:177820 )

• hunched resting posture

hematopoietic system

abnormal spleen trabecular artery morphology ( J:177820 )

• amyloid deposits cause irregular thickening of the arterial walls within the splenic trabeculae

enlarged spleen ( J:177820 )

• due to amyloid deposits and probably also follicular lymphoid hyperplasia and plasmacytosis

• amyloid deposits distort the normal splenic architecture, separating the trabeculae and periarteriolar lymphoid sheaths and expanding the extracellular matrix of the reticular fiber network of the sinusoids

abnormal spleen trabecular vein morphology ( J:177820 )

• amyloid deposits cause irregular thickening of the venous walls within the splenic trabeculae

increased IgG level ( J:74377 )

• mutants without lymphoid neoplasia exhibit an increase in serum polyclonal Ig levels, specifically IgG1 and IgG2b, and the presence of M-components

increased IgG1 level ( J:74377 )

increased IgG2b level ( J:74377 )

cardiovascular system

abnormal spleen trabecular artery morphology ( J:177820 )

• amyloid deposits cause irregular thickening of the arterial walls within the splenic trabeculae

homeostasis/metabolism

amyloidosis ( J:177820 )

• mutants develop spontaneous amyloid protein A (AA) amyloidosis which begins with splenic deposits of AA at 5 months of age and progresses to deposits in the liver, kidney, and vasculature

• however, several mutants develop severe amyloidosis as early as 3 to 5 months of age

growth/size/body

enlarged spleen ( J:177820 )

• due to amyloid deposits and probably also follicular lymphoid hyperplasia and plasmacytosis

• amyloid deposits distort the normal splenic architecture, separating the trabeculae and periarteriolar lymphoid sheaths and expanding the extracellular matrix of the reticular fiber network of the sinusoids

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyloidosis		DOID:9120		J:177820
plasmacytoma		DOID:3721		J:74377