Phenotypes Associated with This Genotype

Genotype
MGI:2655731

• Allelic Composition: Casp8^tm1Raz/Casp8^tm1Raz; Tg(Lck-cre)548Jxm/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

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

mortality/aging

premature death ( J:107455 )

• die at an average age of 51.7 weeks, however lethality is sometimes seen as early as 14 weeks of age

growth/size/body

decreased body size ( J:107455 )

decreased body weight ( J:107455 )

enlarged spleen ( J:107455 )

immune system

enlarged spleen ( J:107455 )

decreased leukocyte cell number ( J:107455 )

• peripheral T cell lymphopenia is seen early in life but is no longer apparent in older mutants

abnormal lymphocyte morphology ( J:107455 )

• peripheral lymphocyte populations from spleens and lymph nodes of old mutants show a decreased B-to-T cell ratio

increased lymphocyte cell number ( J:107455 )

• lymphoproliferation in older mutants is confirmed by increased total lymphocyte counts

increased B cell number ( J:107455 )

• older mutants exhibit a balanced expansion of both B and T lymphocyte numbers in the periphery

abnormal T cell morphology ( J:82759 )

abnormal T cell subpopulation ratio ( J:82759 , J:107455 )

• the CD4+ to CD8+ T-cell ratio is increased in spleen, lymph node, and peripheral blood (J:82759)

• peripheral lymphocyte populations from spleens and lymph nodes of old mutants show a decreased proportion of CD8+ T cells relative to CD4+ T cells (J:107455)

decreased T cell number ( J:82759 )

• relative proportion of splenic and lymph node T cells is significantly lower in young mutants

decreased CD4-positive, alpha-beta T cell number ( J:82759 )

• lower numbers of CD4+ T cells in young mutants

decreased CD8-positive, alpha-beta T cell number ( J:82759 )

• lower numbers of CD8+ T cells in young mutants

increased T cell number ( J:107455 )

• older mutants exhibit a balanced expansion of both B and T lymphocyte numbers in the periphery

abnormal T cell physiology ( J:107455 )

• older mutants accumulate nonclonal T cell infiltrates in the lungs, liver, and kidneys accompanied by tissue damage

• T cell infiltration is seen as early as 20 weeks of age and progresses as mice age

decreased T cell apoptosis ( J:82759 )

• thymocytes and activated T cells are resistant to CD95L-induced apoptosis, however mitochondria-mediated apoptosis is normal

abnormal CD8-positive, alpha-beta T cell physiology ( J:82759 )

• do not exhibit an expansion of CD8+ T cells in the peripheral blood 6 days after lymphocytic choriomeningitis virus (LCMV) infection and show decreased representation of CD62L^highCD44^low (memory) T cells

• LCMV-infected mutants are unable to generate CD8+ cytotoxic T cells specific for LCMV

abnormal T cell activation ( J:107455 )

• isolated T cells from old mutants are in a perpetual state of activation

abnormal T cell proliferation ( J:107455 )

• T cells derived from older mutants exhibit defective in vitro proliferative responses to various stimuli and activated T cells are resistant to CD95L-induced apoptosis

decreased T cell proliferation ( J:82759 )

• exhibit defective activation-induced expansion of peripheral T cells

enlarged lymph nodes ( J:107455 )

• in older mutants

lymphoid hyperplasia ( J:107455 )

• lymphoid hyperplasia is apparent in older mutants

hematopoietic system

enlarged spleen ( J:107455 )

decreased leukocyte cell number ( J:107455 )

• peripheral T cell lymphopenia is seen early in life but is no longer apparent in older mutants

abnormal lymphocyte morphology ( J:107455 )

• peripheral lymphocyte populations from spleens and lymph nodes of old mutants show a decreased B-to-T cell ratio

increased lymphocyte cell number ( J:107455 )

• lymphoproliferation in older mutants is confirmed by increased total lymphocyte counts

increased B cell number ( J:107455 )

• older mutants exhibit a balanced expansion of both B and T lymphocyte numbers in the periphery

abnormal T cell morphology ( J:82759 )

abnormal T cell subpopulation ratio ( J:82759 , J:107455 )

• the CD4+ to CD8+ T-cell ratio is increased in spleen, lymph node, and peripheral blood (J:82759)

• peripheral lymphocyte populations from spleens and lymph nodes of old mutants show a decreased proportion of CD8+ T cells relative to CD4+ T cells (J:107455)

decreased T cell number ( J:82759 )

• relative proportion of splenic and lymph node T cells is significantly lower in young mutants

decreased CD4-positive, alpha-beta T cell number ( J:82759 )

• lower numbers of CD4+ T cells in young mutants

decreased CD8-positive, alpha-beta T cell number ( J:82759 )

• lower numbers of CD8+ T cells in young mutants

increased T cell number ( J:107455 )

• older mutants exhibit a balanced expansion of both B and T lymphocyte numbers in the periphery

abnormal T cell physiology ( J:107455 )

• older mutants accumulate nonclonal T cell infiltrates in the lungs, liver, and kidneys accompanied by tissue damage

• T cell infiltration is seen as early as 20 weeks of age and progresses as mice age

decreased T cell apoptosis ( J:82759 )

• thymocytes and activated T cells are resistant to CD95L-induced apoptosis, however mitochondria-mediated apoptosis is normal

abnormal CD8-positive, alpha-beta T cell physiology ( J:82759 )

• do not exhibit an expansion of CD8+ T cells in the peripheral blood 6 days after lymphocytic choriomeningitis virus (LCMV) infection and show decreased representation of CD62L^highCD44^low (memory) T cells

• LCMV-infected mutants are unable to generate CD8+ cytotoxic T cells specific for LCMV

abnormal T cell activation ( J:107455 )

• isolated T cells from old mutants are in a perpetual state of activation

abnormal T cell proliferation ( J:107455 )

• T cells derived from older mutants exhibit defective in vitro proliferative responses to various stimuli and activated T cells are resistant to CD95L-induced apoptosis

decreased T cell proliferation ( J:82759 )

• exhibit defective activation-induced expansion of peripheral T cells

liver/biliary system

abnormal liver morphology ( J:107455 )

• livers from 30-week old mutants display T cell accumulation as focal perivascular infiltrates

renal/urinary system

abnormal kidney morphology ( J:107455 )

• kidneys from 30-week old mutants show focal interstitial and periglomerular T cell infiltration

respiratory system

abnormal lung morphology ( J:107455 )

• lungs from 30-week old mutants contain obvious interstitial peribronchiovascular T cell infiltration

• at about 1 year of age, disrupted lung tissue organization is associated with much more widespread and abundant T cell infiltration

cellular

decreased T cell apoptosis ( J:82759 )

• thymocytes and activated T cells are resistant to CD95L-induced apoptosis, however mitochondria-mediated apoptosis is normal

abnormal T cell proliferation ( J:107455 )

• T cells derived from older mutants exhibit defective in vitro proliferative responses to various stimuli and activated T cells are resistant to CD95L-induced apoptosis

decreased T cell proliferation ( J:82759 )

• exhibit defective activation-induced expansion of peripheral T cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autoimmune lymphoproliferative syndrome type 2B		DOID:0110116	OMIM:607271	J:107455