Phenotypes Associated with This Genotype

Genotype
MGI:5302497

• Allelic Composition: Tg(Mt1-IL6)28Gci/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

mortality/aging

premature death ( J:18424 , J:177825 )

• mutants die between 2 to 5 months of age, with about 75% dying at 4 months of age (J:18424)

• originally mutants died by 4 months of age, however over time, the renal disease occurring in sucessive generations has become less aggressive and mutants can survive up to 1 year of age (J:177825)

behavior/neurological

hunched posture ( J:18424 , J:177825 )

• mutants develop hunched posture within 3-4 days of death (J:18424)

• hunched posture appears around 8-9 months of age, shortly before death (J:177825)

growth/size/body

weight loss ( J:18424 )

• mutants start to lose weight within 3-4 days of death

enlarged liver ( J:177825 )

enlarged spleen ( J:18424 , J:177825 )

• progressive enlargement of the spleen (J:18424)

immune system

increased leukocyte cell number ( J:18424 )

increased granulocyte number ( J:177825 )

• perivenular granulocytic infiltration is seen in the liver

• granulocytic hyperplasia in the bone marrow and lymph nodes

increased neutrophil cell number ( J:18424 )

• mutants at terminal stages develop neutrophilia (only seen in the last 3-4 days of life)

increased plasmacytoid dendritic cell number ( J:177825 )

• scattered foci of plasmacytoid cells are present in the bone marrow and lymph nodes

• a thick perivascular cuff or plasmacytoid cells surround the renal blood vessel walls

increased plasma cell number ( J:18424 , J:177825 )

• mutants develop plasmacytosis of lymphoid organs (the spleen and lymph nodes), but not in other organs such as the liver, heart or lungs (J:18424)

abnormal spleen morphology ( J:18424 )

• progressive alteration of the spleen, with elevation of megakaryocyte numbers

enlarged spleen ( J:18424 , J:177825 )

• progressive enlargement of the spleen (J:18424)

increased IgG level ( J:18424 , J:177825 )

• IgG hypergammaglobulinemia (J:18424)

increased IgG1 level ( J:18424 )

• increase in polyclonal IgG1 production

increased circulating interleukin-6 level ( J:177825 )

increased circulating serum amyloid protein level ( J:177825 )

• mutants exhibit increased concentrations of serum amyloid A

enlarged lymph nodes ( J:18424 )

• mutants at terminal stages exhibit enlargement of the lymph nodes

renal/urinary system

increased urine protein level ( J:18424 , J:177825 )

• mutants with overt signs of disease exhibit proteinuria, mainly caused by IgG1 (J:18424)

abnormal kidney morphology ( J:18424 )

• mutants at terminal stages exhibit whitening of the kidneys

• kidneys exhibit presence of protein casts in the tubuli and deposition of proteinaceous material

• mutants develop myeloma kidney

expanded mesangial matrix ( J:18424 )

• young animals exhibit an increase in the mesangial matrix of some kidney glomeruli

glomerulosclerosis ( J:18424 )

• older mutants with hypergammaglobulinemia exhibit an increase in the number of damaged glomeruli and develop glomerulosclerosis

renal glomerulus atrophy ( J:177825 )

renal tubule atrophy ( J:18424 )

• mutants that die exhibit tubular atrophy

dilated renal tubule ( J:177825 )

• tubules are dilated and filled with proteinaceous casts

pale kidney ( J:177825 )

kidney failure ( J:18424 , J:177825 )

• mutants exhibit loss of kidney function (J:18424)

homeostasis/metabolism

amyloidosis ( J:177825 )

• mutants exhibit amyloid protein deposits in the spleen, liver, and kidneys by 3 months of age

increased blood urea nitrogen level ( J:18424 , J:177825 )

increased circulating interleukin-6 level ( J:177825 )

increased circulating serum amyloid protein level ( J:177825 )

• mutants exhibit increased concentrations of serum amyloid A

pulmonary edema ( J:18424 )

• mutants at terminal stages exhibit increased volume and clear signs of edema of the lungs

increased urine protein level ( J:18424 , J:177825 )

• mutants with overt signs of disease exhibit proteinuria, mainly caused by IgG1 (J:18424)

hematopoietic system

extramedullary hematopoiesis ( J:177825 )

increased megakaryocyte cell number ( J:18424 , J:177825 )

• increase in the number of megakaryocytes in the spleen and bone marrow (J:18424)

• megakaryocytic hyperplasia in the bone marrow and lymph nodes (J:177825)

increased mean platelet volume ( J:18424 )

increased leukocyte cell number ( J:18424 )

increased granulocyte number ( J:177825 )

• perivenular granulocytic infiltration is seen in the liver

• granulocytic hyperplasia in the bone marrow and lymph nodes

increased neutrophil cell number ( J:18424 )

• mutants at terminal stages develop neutrophilia (only seen in the last 3-4 days of life)

increased plasmacytoid dendritic cell number ( J:177825 )

• scattered foci of plasmacytoid cells are present in the bone marrow and lymph nodes

• a thick perivascular cuff or plasmacytoid cells surround the renal blood vessel walls

increased plasma cell number ( J:18424 , J:177825 )

• mutants develop plasmacytosis of lymphoid organs (the spleen and lymph nodes), but not in other organs such as the liver, heart or lungs (J:18424)

abnormal spleen morphology ( J:18424 )

• progressive alteration of the spleen, with elevation of megakaryocyte numbers

enlarged spleen ( J:18424 , J:177825 )

• progressive enlargement of the spleen (J:18424)

increased IgG level ( J:18424 , J:177825 )

• IgG hypergammaglobulinemia (J:18424)

increased IgG1 level ( J:18424 )

• increase in polyclonal IgG1 production

respiratory system

pulmonary edema ( J:18424 )

• mutants at terminal stages exhibit increased volume and clear signs of edema of the lungs

liver/biliary system

enlarged liver ( J:177825 )

skeleton

decreased bone mineral density ( J:177825 )

• bones are fragile with osteopenia

decreased compact bone thickness ( J:177825 )

• thin cortices

abnormal trabecular bone morphology ( J:177825 )

• loss of cancellous bone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyloidosis		DOID:9120		J:177825