immune system
• mice exhibit pronounced spleen hypertrophy compared with wild-type mice
• however, cellular architecture is preserved
|
• average spleen weight is ~5x that of wild-type controls
|
• most mice exhibit cryoglobulins positive for IgG1, IgM, and kappa and lambda chains
• mice develop polyclonal mixed cryoglobulinemia
|
• in 11 of 25 mice
|
• mice develop cryoglobulinemic membranoproliferative type glomerulonephritis that is more severe in female mice than in male mice
|
• lungs exhibit perivascular leukocyte infiltration unlike in wild-type mice
• lung inflammation becomes severe
|
renal/urinary system
• subendothelial deposits, cellular interposition and splitting of capillary walls
• leukocytes found in capillary lumina, some adhering to endothelial cells, others infiltrating the mesangium
• capillary walls are thickened, sometimes with prominent double contours of the capillary walls
• PAS-positive deposits detected in capillary walls, leading to intracapillary globular thrombi and complete capillary occlusion in severe cases
• number of patent capillary lumina decreases as diseases progresses
• however, no leukocytic infiltrates are detected in arterial walls
|
• endothelial cells covering the immune deposits show signs of activation, with cellular swelling and absence of normal pores
|
• endothelial cells covering the immune deposits lack normal pores
|
albuminuria
(
J:72982
)
• significant increase in albumin excretion in both sexes; the albumin to creatinine ratio is increased 2.5-fold in male mice and 5-fold in female mice compared to in wild-type mice
|
• mice develop cryoglobulinemic membranoproliferative type glomerulonephritis that is more severe in female mice than in male mice
|
• seen in areas of capillary walls involved by immune deposits
|
• both sexes show widening of the mesangial area at 1 month of age; due to an increase in mesangial matrix and mesangial deposits of immune complexes
• PAS-positive deposits detected in the mesangium
|
• increase in mesangial matrix at >1 month of age
• more prominent in females at early time points (1 to 2 months of age) than in males
|
• increased glomerular size with an absolute increase in the cell number per glomerulus
• accentuated lobular appearance of the glomerular tuft architecture is often observed
• however, globally sclerotic glomeruli are absent and the tubulointerstitium remains unaffected with no significant inflammation or fibrosis
|
• glomeruli exhibit expansion of the mesangium due to increased matrix and accumulation of immuno-deposits, subendothelial immune-deposits, focal occlusion of capillary loops, and monocyte/macrophage influx unlike in wild-type mice
|
respiratory system
• lungs exhibit perivascular leukocyte infiltration unlike in wild-type mice
• lung inflammation becomes severe
|
cardiovascular system
• capillary walls are thickened, sometimes with prominent double contours of the capillary walls
• PAS-positive deposits detected in capillary walls, leading to intracapillary globular thrombi and complete capillary occlusion in severe cases
• number of patent capillary lumina decreases as diseases progresses
• subendothelial deposits, cellular interposition and splitting of capillary walls
• leukocytes found in capillary lumina, some adhering to endothelial cells, others infiltrating the mesangium
• however, no leukocytic infiltrates are detected in arterial walls
|
• endothelial cells covering the immune deposits show signs of activation, with cellular swelling and absence of normal pores
|
• endothelial cells covering the immune deposits lack normal pores
|
• in some mice
|
growth/size/body
• in some mice
|
• in female mice
|
• mice exhibit pronounced spleen hypertrophy compared with wild-type mice
• however, cellular architecture is preserved
|
• average spleen weight is ~5x that of wild-type controls
|
homeostasis/metabolism
• small but significant increase in blood urea nitrogen in both sexes
|
• PAS-positive deposits detected in capillary walls, leading to intracapillary globular thrombi and complete capillary occlusion in severe cases
|
albuminuria
(
J:72982
)
• significant increase in albumin excretion in both sexes; the albumin to creatinine ratio is increased 2.5-fold in male mice and 5-fold in female mice compared to in wild-type mice
|
hematopoietic system
• mice exhibit pronounced spleen hypertrophy compared with wild-type mice
• however, cellular architecture is preserved
|
• average spleen weight is ~5x that of wild-type controls
|
• most mice exhibit cryoglobulins positive for IgG1, IgM, and kappa and lambda chains
• mice develop polyclonal mixed cryoglobulinemia
|
liver/biliary system
integument
• 22% of male and 4% of female mice develop progressive ulcerative lesions of the ears
|
cellular
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
cryoglobulinemia | DOID:2917 | J:72982 | ||
membranoproliferative glomerulonephritis | DOID:2920 |
OMIM:305800 |
J:72982 |