Phenotypes Associated with This Genotype

Genotype
MGI:3707331

• Allelic Composition: Tusc2^tm1Avi/Tusc2^tm1Avi
• Genetic Background: involves: 129S1/Sv * C57BL/6J

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

mortality/aging

premature death ( J:119985 )

• 11% of mice die between 2 and 14 months of age; some show signs of systemic infection, whereas others show necrotizing arteritis in multiple organs, severe glomerulonephrits, severe nephropathy, and anemia

• some animals develop tumors and die prematurely

growth/size/body

decreased body weight ( J:119985 )

• homozygous mice show an ~20% reduction in body weight compared to wild-type by 6 months of age

cardiovascular system

vascular inflammation ( J:119985 )

• some mice show a vasculitis syndrome

arteritis ( J:119985 )

• 20% of mice dying before or sacrificed at 2 years of age develop arteritis in single or multiple organs

• arteritis is found in large vessels and small arteries, veins and capillaries

• multiple organs like the heart, kidney, liver, lung pancreas, spleen, lymph nodes, thyroid, gall bladder, tongue, spinal cord muscles, and omentum show arteritis; some mice develop necrotizing arteritis in pancreas, liver, spleen, small intestine, ovary, uterus, urethra, and spinal cord

• some arteritic lesions show infiltration of entire vessel with fibrinoid necrosis

hematopoietic system

abnormal NK cell differentiation ( J:119985 )

• a decreased percentage of NK cells expressing Ly49G is seen in the liver (57%) and spleen (35%) indicating maturation is defective, with a blockade at the immature CD94^bright stage

decreased erythrocyte cell number ( J:119985 )

• 3 mice showing arteritis and/or glomerulonephritis had low red blood cell counts

decreased NK cell number ( J:119985 )

• at 4 weeks of age, a 45% decrease in total number of NK cells compared to controls is observed; in spleen, decrease is ~56%, while in bone marrow it is ~45%; there is no difference in the liver

increased leukocyte cell number ( J:119985 )

• 2 mice showing arteritis and/or glomerulonephritis had dramatically elevated white blood cell counts

immune system

arteritis ( J:119985 )

• 20% of mice dying before or sacrificed at 2 years of age develop arteritis in single or multiple organs

• arteritis is found in large vessels and small arteries, veins and capillaries

• multiple organs like the heart, kidney, liver, lung pancreas, spleen, lymph nodes, thyroid, gall bladder, tongue, spinal cord muscles, and omentum show arteritis; some mice develop necrotizing arteritis in pancreas, liver, spleen, small intestine, ovary, uterus, urethra, and spinal cord

• some arteritic lesions show infiltration of entire vessel with fibrinoid necrosis

abnormal NK cell differentiation ( J:119985 )

• a decreased percentage of NK cells expressing Ly49G is seen in the liver (57%) and spleen (35%) indicating maturation is defective, with a blockade at the immature CD94^bright stage

decreased NK cell number ( J:119985 )

• at 4 weeks of age, a 45% decrease in total number of NK cells compared to controls is observed; in spleen, decrease is ~56%, while in bone marrow it is ~45%; there is no difference in the liver

increased leukocyte cell number ( J:119985 )

• 2 mice showing arteritis and/or glomerulonephritis had dramatically elevated white blood cell counts

decreased interleukin-15 secretion ( J:119985 )

• Il15 production is decreased compared to wild-type

increased susceptibility to autoimmune disorder ( J:119985 )

• some mice which died prematurely showed arteritis, severe kidney abnormalities and anemia which are hallmarks of autoimmune disorder whereas wild-type mice did not display any of these

increased anti-nuclear antigen antibody level ( J:119985 )

• circulating autoreactive nuclear antibodies are detected

glomerulonephritis ( J:119985 )

• severe glomerulonephritis sometimes associated with extensive tubular cast formation

neoplasm

abnormal tumor incidence ( J:119985 )

• no distinct tumor pattern is observed in organs outside the hematopoietic system

increased hemangioma incidence ( J:119985 )

• ~32% of mice develop mixed hemangioma/hemangiosarcoma or either independently compared to ~4% in wild-type; females are most susceptible to these tumor types

increased lymphoma incidence ( J:119985 )

• 1 mouse developed lymphoma at 7 months of age

increased squamous cell carcinoma incidence ( J:119985 )

• one mouse developed an invasive squamous cell skin carcinoma at 13 months of age

increased hemangiosarcoma incidence ( J:119985 )

renal/urinary system

abnormal renal glomerulus morphology ( J:119985 )

• glomerular lesions often include membranoproliferative changes, wire-loop-like subendothelial deposits, and intracapillary thrombi that often obstruct the capillary lumen

glomerulonephritis ( J:119985 )

• severe glomerulonephritis sometimes associated with extensive tubular cast formation

renal cast ( J:119985 )

• extensive tubular cast formation

homeostasis/metabolism

abnormal glomerular capillary thrombosis ( J:119985 )

adipose tissue

adipose tissue necrosis ( J:119985 )

• one mice presenting a vasculitis syndrome developed fat necrosis