Mouse Genome Informatics
cn
    Casp8tm1Raz/Casp8tm1Raz
Tg(Lck-cre)548Jxm/0

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• die at an average age of 51.7 weeks, however lethality is sometimes seen as early as 14 weeks of age

growth/size/body

immune system
• peripheral T cell lymphopenia is seen early in life but is no longer apparent in older mutants
• peripheral lymphocyte populations from spleens and lymph nodes of old mutants show a decreased B-to-T cell ratio
• lymphoproliferation in older mutants is confirmed by increased total lymphocyte counts
• older mutants exhibit a balanced expansion of both B and T lymphocyte numbers in the periphery
• 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)
• relative proportion of splenic and lymph node T cells is significantly lower in young mutants
• lower numbers of CD4+ T cells in young mutants
• lower numbers of CD8+ T cells in young mutants
• older mutants exhibit a balanced expansion of both B and T lymphocyte numbers in the periphery
• isolated T cells from old mutants are in a perpetual state of activation
• 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
• exhibit defective activation-induced expansion of peripheral T cells
• 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
• thymocytes and activated T cells are resistant to CD95L-induced apoptosis, however mitochondria-mediated apoptosis is normal
• 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 CD62LhighCD44low (memory) T cells
• LCMV-infected mutants are unable to generate CD8+ cytotoxic T cells specific for LCMV
• lymphoid hyperplasia is apparent in older mutants
• in older mutants

hematopoietic system
• peripheral T cell lymphopenia is seen early in life but is no longer apparent in older mutants
• peripheral lymphocyte populations from spleens and lymph nodes of old mutants show a decreased B-to-T cell ratio
• lymphoproliferation in older mutants is confirmed by increased total lymphocyte counts
• older mutants exhibit a balanced expansion of both B and T lymphocyte numbers in the periphery
• 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)
• relative proportion of splenic and lymph node T cells is significantly lower in young mutants
• lower numbers of CD4+ T cells in young mutants
• lower numbers of CD8+ T cells in young mutants
• older mutants exhibit a balanced expansion of both B and T lymphocyte numbers in the periphery
• isolated T cells from old mutants are in a perpetual state of activation
• 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
• exhibit defective activation-induced expansion of peripheral T cells
• 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
• thymocytes and activated T cells are resistant to CD95L-induced apoptosis, however mitochondria-mediated apoptosis is normal
• 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 CD62LhighCD44low (memory) T cells
• LCMV-infected mutants are unable to generate CD8+ cytotoxic T cells specific for LCMV

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

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

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

Mouse Models of Human Disease
OMIM IDRef(s)
CASPase 8 Deficiency 607271 J:107455