Mouse Genome Informatics
hm1
    Prf1tm1Sdz/Prf1tm1Sdz
C.B6-Prf1tm1Sdz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• some lymphomas have an unusual histiocytic appearance with a pale eosinophilic cytoplasm
• some mice develop disseminated lymphomas
• in a few mice, with a very late onset
• all are well differentiated papillary adenocarcinomas
• in a few mice
• in mice on a BALB/c background compared to mice on a C57BL/6 background


Mouse Genome Informatics
hm2
    Prf1tm1Sdz/Prf1tm1Sdz
C57BL/6-Prf1tm1Sdz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die between 40 and 60 days after injection of 10^7 MHC class-I deficient B cell lymphoma cells, while all wild-type mice survive
• Background Sensitivity: in mice on a C57BL/6 background compared to mice on a BALB/c background

immune system
• impaired ability to clear injected MHC class-I deficient B cell lymphoma cells resulting in increased mortality
• NK-cell-mediated lysis is not evident in the spleen cells after viral infection
• CD8+ T cells cannot lyse in vitro virus-infected, peptide-coated or allogeneic target cells of epithelial, neuroectodermal or mesodermal orgin, however activation and expansion of CD8+ T cells occurs normally
• following infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), IL-10 production is increased relative to infected wild-type mice
• fail to develop footpad swelling upon lymphocytic choriomeningitis virus injection into the footpad
• following infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), mice have a higher burden of bacteria in the liver and lungs but not spleens, develop extensive partially confluent foci of apoptosis or necrosis of contiguous hepatocytes with mild to moderate liver injury, and more macrophage-rich inflammatory infiltrates compared to infected wild-type mice
• following infection with IOE, IL-10 production is increased relative to infected wild-type mice
• decreased clearance and survival after infection with Trypanosoma cruzi
• unable to eliminate lymphocytic choriomeningitis virus 12 days after intravenous infection as in controls, with infection eventually leading to weight loss and death between days 13 and 16

reproductive system
• alpha-galactosylceramide induced abortion does not occur (J:59892)

tumorigenesis
• develop aggressive disseminated lymphomas that affect the spleen, liver and lymph nodes from 300 days of age onwards
• most lymphomas are diffuse large cell lymphomas
• lymphomas are of a B cell origin or plasmocytomas
• Background Sensitivity: in mice on a C57BL/6 background compared to mice on a BALB/c background

hematopoietic system
• impaired ability to clear injected MHC class-I deficient B cell lymphoma cells resulting in increased mortality
• NK-cell-mediated lysis is not evident in the spleen cells after viral infection
• CD8+ T cells cannot lyse in vitro virus-infected, peptide-coated or allogeneic target cells of epithelial, neuroectodermal or mesodermal orgin, however activation and expansion of CD8+ T cells occurs normally


Mouse Genome Informatics
hm3
    Prf1tm1Sdz/Prf1tm1Sdz
C57BL/6-Prf1tm1Sdz/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants die within 2 weeks of lymphocytic choriomeningitic virus (LCMV) infection unlike wild-type mice (J:92260)
• mutants depleted of CD8+ cells (by administration of antibodies against CD8+ cells) survive LCMV infection, however those depleted of CD4+ or NK cells do not survive (J:92260)
• neutralizing multiple cytokines, including TNF-alpha, IL-12, IL-18, M-CSF, and GM-CSF, with neutralizing antibodies has no effect on survival (J:92260)
• mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias (J:92260)
• mice die 2 weeks after LCMV infection (J:193137)

nervous system
• by 7 days after TMEV infection, inflammation is present in the meninges and gray matter of spinal cords in controls as well
• by 21 days, inflammation with macrophage infiltration persists in the gray matter in mutants but not in controls
• 30 days after LCMV infection, the meninges show prominent mononuclear infiltrates along the dura (J:92260)
• by 7 days after TMEV infection, inflammation is present, decreasing slightly by 21 days, but widespread tissue damage is present, similar to controls (B6) (J:120427)
• by 45 days, inflammation with parenchymal disease is seen in hippocampus, striatum, and corpus callosum in some mice (J:120427)
• persistent inflammation is found in the brainstem of mutants (J:120427)
• at 180 days, brain pathology is still present (J:120427)
• 30 days after LCMV infection, the meninges show prominent mononuclear infiltrates along the dura
• at 45 days after infection, foci of demyelination are observed in spinal cord (in 11% of 537 quadrants examined)
• lesions are located mainly in the anterior and anterolateral white matter of the spinal cord; demyelination is chronic and progressive (16% of quadrants at 90 days and 20% of quadrants at 180 days)
• demyelinated axons in close proximity to inflammatory cells and macrophages with intracytoplasmic vacuoles containing myelin debris are seen in mutants, but not in control or other null mice

immune system
N
• delayed type hypersensitivity (DTH) reaction elicited in the ear by intradermal injection of inactive virus is comparable to that of controls (J:120427)
• in LMCV-infected mice
• lack of neutrophilia in LMCV-infected mice
• by 10-12 days after LCMV infection, red pulp is expanded when compared to wild-type mice
• by 10-12 days after LCMV infection, the white pulp appears chaotic with a prominent infiltrate of macrophages and activated lymphocytes when compared to wild-type spleen
• CNS-infiltrating mononuclear cells have impaired lytic activity LP- and VP2-transfected target cells in vitro (TMEV leader peptide and VP2 capsid protein), in contrast to effective lysis demonstrated by control cells
• mutants exhibit an elevation of antigen-specific CD8+ T and CD4+ T cells in the bone marrow, liver, and spleen following LCMV infection compared to wild-type mice
• in the presence of recombinant IL15 alone or in combination with IL2
• impaired CD8+ T cell degranulation
• however, priming is normal
• reduced killing of anti-CD3-loaded P815 target cells, more pronounced than in than in Rab27aash and Stx11tm1.2Ics cells
• hemophagocytic macrophages are seen in lymph node, spleen, liver and bone marrow tissues of LCMV infected mutants unlike in wild-type mice
• mutants exhibit elevated serum levels of IFN-alpha at 6-8 days after LCMV infection unlike wild-type mice which show peak IFN-alpha levels at day 3 of infection and undetectable levels by 4-5 days of infection
• mutants exhibit elevated (10- to 100-fold) and prolonged serum levels of IFN-gamma following LCMV infection compared to wild-type mice (J:92260)
• mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias (J:92260)
• in LMCV-infected mice (J:193137)
• increased at 12 days after LCMV infection compared to wild-type mice
• increased at 12 days after LCMV infection compared to wild-type mice
• increased at 12 days after LCMV infection compared to wild-type mice (J:92260)
• in LMCV-infected mice (J:193137)
• increased at 12 days after LCMV infection compared to wild-type mice (J:92260)
• in LMCV-infected mice (J:193137)
• 8-10 days after LCMV infection, mutants develop hypofibrinogenemia compared to wild-type controls
• by 10-12 days after LCMV infection, lymph node architecture is deranged with disorganized macrophage and activated lymphocyte infiltrates replacing the normal follicular structure of lymph nodes and some lymph nodes exhibit necrotic changes compared to wild-type mice
• by 10-12 days after LCMV infection, lymph node architecture is deranged with disorganized macrophage and activated lymphocyte infiltrates replacing the normal follicular structure
• IFN-gamma production by CD8+ T cells is less on a per-cell basis in response to both peptide and anti-CD3 stimulation after LCMV infection compared with wild-type mice, however the number of spontaneously IFN-gamma producing (without stimulation) CD8+ T cells is increased, indicating that ongoing antigenic stimulation results in the increased cytokine secretion
• by 7 days after TMEV infection, inflammation is present in the meninges and gray matter of spinal cords in controls as well
• by 21 days, inflammation with macrophage infiltration persists in the gray matter in mutants but not in controls
• 30 days after LCMV infection, the meninges show prominent mononuclear infiltrates along the dura (J:92260)
• by 7 days after TMEV infection, inflammation is present, decreasing slightly by 21 days, but widespread tissue damage is present, similar to controls (B6) (J:120427)
• by 45 days, inflammation with parenchymal disease is seen in hippocampus, striatum, and corpus callosum in some mice (J:120427)
• persistent inflammation is found in the brainstem of mutants (J:120427)
• at 180 days, brain pathology is still present (J:120427)
• by 10-12 days after LCMV infection, livers show prominent periportal infiltrates
• mutants cannot clear lymphocytic choriomeningitic virus (LCMV) infection like wild-type mice can (J:92260)
• inflammation and tissue damage in the brain are greater than in control, resistant mice at 45 and 180 days (J:120427)
• at 45 days, viral mRNA is still detected in spinal cords of mutants but not in controls or Fas and Fasl mutants (J:120427)
• LMCV-infected mice develop clinical features of hemophagocytic lymphohistiocytosis including weight loss, body temperature drop, hunched posture, lethargy, pancytopenia, lack of neutrophilia, increased circulating aspartate transaminase level, increased circulating lactate dehydrogenase level, increased serum levels of IFN-gamma, IL1b, TNF-alpha and IL6, increased viral load and worsening condition compared with wild-type mice (J:193137)
• LMCV-infected mice develop more severe hemophagocytic lymphohistiocytosis than in Rab27aash and Stx11tm1.2Ics homozygotes despite similar viral loads (J:193137)
• mutants die within 2 weeks of lymphocytic choriomeningitic virus (LCMV) infection unlike wild-type mice (J:92260)
• mutants depleted of CD8+ cells (by administration of antibodies against CD8+ cells) survive LCMV infection, however those depleted of CD4+ or NK cells do not survive (J:92260)
• neutralizing multiple cytokines, including TNF-alpha, IL-12, IL-18, M-CSF, and GM-CSF, with neutralizing antibodies has no effect on survival (J:92260)
• mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias (J:92260)
• mice die 2 weeks after LCMV infection (J:193137)

behavior/neurological
N
• mice infected with TMEV and monitored daily do not show clinical signs of TMEV infecion, including unkempt appearance, decreased spontaneous movement and hind-limb paralysis, at 45 days and 90 days, whereas 12% of susceptible SJL mice show clinical disease at 90 days and 64% by 180 days (J:120427)
• some chronically infected mice demonstrate minor alterations in stride with normal activity levels, despite presence of demyelination
• mutants infected with LCMV display hunched posture 10 days after infection unlike wild-type mice (J:92260)
• in LMCV-infected mice (J:193137)
• mutants infected with lymphocytic choriomeningitic virus (LCMV) display decreased activity 10 days after infection compared with wild-type controls
• in LMCV-infected mice

hematopoietic system
• in LMCV-infected mice
• in LMCV-infected mice
• lack of neutrophilia in LMCV-infected mice
• in LMCV-infected mice
• unlike wild-type mice, mutants become pancytopenic by 10 days after LCMV infection (J:92260)
• in LMCV-infected mice (J:193137)
• bone marrow shows severe hypoplasia by 10-12 days after LCMV infection when compared to wild-type mice
• by 10-12 days after LCMV infection, red pulp is expanded when compared to wild-type mice
• by 10-12 days after LCMV infection, the white pulp appears chaotic with a prominent infiltrate of macrophages and activated lymphocytes when compared to wild-type spleen
• CNS-infiltrating mononuclear cells have impaired lytic activity LP- and VP2-transfected target cells in vitro (TMEV leader peptide and VP2 capsid protein), in contrast to effective lysis demonstrated by control cells
• mutants exhibit an elevation of antigen-specific CD8+ T and CD4+ T cells in the bone marrow, liver, and spleen following LCMV infection compared to wild-type mice
• in the presence of recombinant IL15 alone or in combination with IL2
• impaired CD8+ T cell degranulation
• however, priming is normal
• reduced killing of anti-CD3-loaded P815 target cells, more pronounced than in than in Rab27aash and Stx11tm1.2Ics cells
• hemophagocytic macrophages are seen in lymph node, spleen, liver and bone marrow tissues of LCMV infected mutants unlike in wild-type mice

homeostasis/metabolism
• 8-10 days after LCMV infection, mutants develop hypertriglyceridemia compared to wild-type controls
• mutants exhibit elevated serum levels of IFN-alpha at 6-8 days after LCMV infection unlike wild-type mice which show peak IFN-alpha levels at day 3 of infection and undetectable levels by 4-5 days of infection
• mutants exhibit elevated (10- to 100-fold) and prolonged serum levels of IFN-gamma following LCMV infection compared to wild-type mice (J:92260)
• mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias (J:92260)
• in LMCV-infected mice (J:193137)
• increased at 12 days after LCMV infection compared to wild-type mice
• increased at 12 days after LCMV infection compared to wild-type mice
• increased at 12 days after LCMV infection compared to wild-type mice (J:92260)
• in LMCV-infected mice (J:193137)
• increased at 12 days after LCMV infection compared to wild-type mice (J:92260)
• in LMCV-infected mice (J:193137)
• 8-10 days after LCMV infection, mutants develop hypofibrinogenemia compared to wild-type controls
• in LMCV-infected mice
• while wild-type mice infected with LCMV develop a brief febrile response early after infection, mutants exhibit a prolonged temperature elevation that is still seen at 10 days after infection

integument
• mutants infected with LCMV display ruffled fur 10 days after infection when compared with wild-type controls

liver/biliary system
• by 10-12 days after LCMV infection, livers show prominent periportal infiltrates

growth/size
• in LMCV-infected mice


Mouse Genome Informatics
hm4
    Prf1tm1Sdz/Prf1tm1Sdz
involves: BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• activated splenic NK cells are unable to kill 4T1 or Renca tumor target cells

hematopoietic system
• activated splenic NK cells are unable to kill 4T1 or Renca tumor target cells


Mouse Genome Informatics
hm5
    Prf1tm1Sdz/Prf1tm1Sdz
NOD.B6-Prf1tm1Sdz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• after cyclophosphamide treatment, perforin-null NOD mice display temporary hyperglycemia but return to normoglycemia while control NOD mice become hyperglycemic and often die as a result
• cyclophosphamide treatment of 8-12 week old NOD control and perforin-heterozygous NOD mice on day 0 and 12 induces diabetes at an incidence of 80-90% after the second treatment between 24 and 30 days, while diabetes occurs in 18% of homozygous NOD mutants between 32 and 38 days

endocrine/exocrine glands
• diabetic perforin-null mice have a drastically reduced volume density of endocrine islet tissue (beta cells) compared with 7-week old control NOD mice
• at 8 weeks of age, insulitis is seen to varying degrees in perforin-null and heterozygous mice; by 55 weeks of age, in non-diabetic null mice, severe insulitis develops with a higher frequency than in perforin-expressing NOD controls
• periinsulitis is observed in 8-week old perforin-null and heterozygous mice with little islet cell damage, compared to detection at 5 weeks in control NOD mice

immune system
• at 8 weeks of age, insulitis is seen to varying degrees in perforin-null and heterozygous mice; by 55 weeks of age, in non-diabetic null mice, severe insulitis develops with a higher frequency than in perforin-expressing NOD controls
• periinsulitis is observed in 8-week old perforin-null and heterozygous mice with little islet cell damage, compared to detection at 5 weeks in control NOD mice
• female perforin-null NOD mice show significantly decrease incidence of diabetes (16%) with a delayed onset between 35 and 41 weeks, while control NOD mice, diabetes occurred between 15 and 30 weeks of age with an incidence of 77%; male control NOD mice show less than 20% incidence of diabetes, while no null NOD mice develop diabetes


Mouse Genome Informatics
ht6
    Prf1tm1Sdz/Prf1+
NOD.B6-Prf1tm1Sdz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 8 weeks of age, insulitis is seen to varying degrees in perforin-null and heterozygous mice; by 55 weeks of age, in non-diabetic null mice, severe insulitis develops with a higher frequency than in perforin- expressing NOD controls
• periinsulitis is observed in 8-week old perforin-null and heterozygous mice with little islet cell damage, compared to detection at 5 weeks in control NOD mice
• female heterozygous NOD mice show a delayed incidence (median: week 27) in development of diabetes (determined by high blood glucose) with an incidence of 67% compared to early onset (median: week 19) with an incidence of 77% in control NOD mice

endocrine/exocrine glands
• at 8 weeks of age, insulitis is seen to varying degrees in perforin-null and heterozygous mice; by 55 weeks of age, in non-diabetic null mice, severe insulitis develops with a higher frequency than in perforin- expressing NOD controls
• periinsulitis is observed in 8-week old perforin-null and heterozygous mice with little islet cell damage, compared to detection at 5 weeks in control NOD mice


Mouse Genome Informatics
cx7
    Gzmatm1Simn/Gzmatm1Simn
Gzmbtm1Ley/Gzmbtm1Ley
Prf1tm1Sdz/Prf1tm1Sdz

B6.Cg-Gzmatm1Simn Gzmbtm1Ley Prf1tm1Sdz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• WNV-infected triple homozygotes display prolonged mean survival time (MST) but significantly increased mortality (50%) relative to either wild-type (29%) or Prf1tm1Sdz (18%) mice

immune system
N
• triple homozygotes develop a normal contact hypersensitivity (CHS) response (based on increase in ear thickness) to trinitrophenyl (TNP) relative to wild-type mice (J:92718)
• decreased clearance and survival after infection with Trypanosoma cruzi
• triple homozygotes display increased susceptibility to West Nile flavivirus (WNV) infection relative to wild-type
• triple mutants show a higher level of infectious virus in brain relative to wild-type or Prf1tm1Sdz mice at the same time point


Mouse Genome Informatics
cx8
    Ifngtm1Ts/Ifngtm1Ts
Prf1tm1Sdz/Prf1tm1Sdz

C.Cg-Prf1tm1Sdz Ifngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

tumorigenesis
• some lymphomas have an unusual histiocytic appearance with a pale eosinophilic cytoplasm
• incidence is increased and onset is earlier compared to mice homozygous for Prf1tm1Sdz alone
• incidence is increased and onset is earlier compared to mice homozygous for Prf1tm1Sdz alone


Mouse Genome Informatics
cx9
    Bmgr2C57BL/6J/?
Prf1tm1Sdz/Prf1tm1Sdz

involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• increased NK cell-mediated bone marrow graft rejection


Mouse Genome Informatics
cx10
    Bmgr3129S6/SvEvTac/Bmgr3129S6/SvEvTac
Prf1tm1Sdz/Prf1tm1Sdz

involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• increased NK cell-mediated bone marrow graft rejection


Mouse Genome Informatics
cx11
    Bmgr4C57BL/6J/?
Prf1tm1Sdz/Prf1tm1Sdz

involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• increased NK cell-mediated bone marrow graft rejection


Mouse Genome Informatics
cx12
    Bmgr4C57BL/6J/?
Ebmgr1129S6/SvEvTac/Ebmgr1129S6/SvEvTac
Prf1tm1Sdz/Prf1tm1Sdz

involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• increased NK cell-mediated bone marrow graft rejection


Mouse Genome Informatics
cx13
    Ins2Akita/Ins2Akita
Prf1tm1Sdz/Prf1tm1Sdz
Rag1tm1Mom/Rag1tm1Mom

NOD.Cg-Rag1tm1Mom Ins2Akita Prf1tm1Sdz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die prior to weaning


Mouse Genome Informatics
cx14
    Ins2Akita/Ins2+
Prf1tm1Sdz/Prf1tm1Sdz
Rag1tm1Mom/Rag1tm1Mom

NOD.Cg-Rag1tm1Mom Ins2Akita Prf1tm1Sdz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• islets exhibit progressively altered morphology
• insulin level is lower compared to Ins2-wild-type mice at 50 days of age and continues to diminish with age

hematopoietic system
• erythrocyte/erythocyte lineages (Ter 119+) are increased as compared to NOD controls
• percentage of granulocytes is elevated compared to NOD/Lt
• lacking in mutant animals
• mature T cells are absent in mutant animals
• percentage of granulocytes is elevated
• percentage of granulocytes is elevated

immune system
• percentage of granulocytes is elevated compared to NOD/Lt
• lacking in mutant animals
• mature T cells are absent in mutant animals
• percentage of granulocytes is elevated
• percentage of granulocytes is elevated

homeostasis/metabolism
N
• spontaneously hyperglycemic mice are restored to euglycemia after receiving islet transplants at a dose of 4000 islet equivalents (IEQ) and remain euglycemic for the length of observation; at levels of 2000 and 3000 IEQ, mice display a drop in blood sugar, but eventually return to hyperglycemic status (J:138005)
• glucose regulation is impaired as early as 3 weeks of age in nearly all mice
• male mice show greater susceptibility to develop hyperglycemia than females


Mouse Genome Informatics
cx15
    Rag1tm1Mom/Rag1tm1Mom
Prf1tm1Sdz/Prf1tm1Sdz

NOD.Cg-Rag1tm1Mom Prf1tm1Sdz/Sz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mean lifespan is 262+/-21 days

immune system
• thymus lacks a clearly defined cortex
• lymphoid cells are severely reduced in thymuses
• numbers of granulocytes are increased in comparison to NOD controls, however, in comparison to NOD-Ragnull numbers are decreased
• spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells
• IgLkappa- B220+ immature B cells are increased six-fold as compared to NOD controls
• numbers of NK cells are increased in comparison to NOD controls
• spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells
• spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells
• numbers of macrophages are increased in comparison to NOD controls
• nucleated spleen cells are reduced 14 fold in 8-11 week old mice as compared to NOD control
• spleen lacks lymphoid follicles
• four to five-fold decrease in cells expressing I-Ag7 as compared to NOD control
• no serum immunoglobulin is detected in 176-362 day old mice
• poly I:C stimulated spleen cells exhibit extremely low levels of NK cell cyotoxic activity
• lymph nodes lack follicles
• following IP injection of human PMBC, peripheral blood has a fivefold increase in the percentage of human lymphoid cells as compared to NOD-Ragnull controls
• peripheral blood has a 13-fold increase in engraftment of human CD4+ T cells
• spleens have a 9-fold increase in engraftment of human CD45+ cells and a 20-fold increase in human CD4+ cells as compared to control, although there is no significant difference in engraftment of human CD8+ cells
• 6-8 weeks after IP injection, bone marrow exhibits a 12-fold increase in engraftment of human cord blood cells

tumorigenesis

hematopoietic system
• thymus lacks a clearly defined cortex
• lymphoid cells are severely reduced in thymuses
• numbers of granulocytes are increased in comparison to NOD controls, however, in comparison to NOD-Ragnull numbers are decreased
• spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells
• IgLkappa- B220+ immature B cells are increased six-fold as compared to NOD controls
• numbers of NK cells are increased in comparison to NOD controls
• spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells
• spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells
• numbers of macrophages are increased in comparison to NOD controls
• nucleated spleen cells are reduced 14 fold in 8-11 week old mice as compared to NOD control
• spleen lacks lymphoid follicles
• four to five-fold decrease in cells expressing I-Ag7 as compared to NOD control
• no serum immunoglobulin is detected in 176-362 day old mice
• poly I:C stimulated spleen cells exhibit extremely low levels of NK cell cyotoxic activity

endocrine/exocrine glands
• thymus lacks a clearly defined cortex
• lymphoid cells are severely reduced in thymuses


Mouse Genome Informatics
cx16
    Prf1tm1Sdz/Prf1tm1Sdz
Rag1tm1Mom/Rag1tm1Mom

NOD.Cg-Rag1tm1Mom Prf1tm1Sdz/SzJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• streptozotocin-treated mice exhibit increased serum glucose levels that can be restored transiently to euglycemia by transplanting islet cells from Prkdcscid/Prkdcscid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice
• 70% of streptozotocin-treated mice transplanted with islet cells from Prkdcscid/Prkdcscid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 negative human peripheral blood mononuclear cells exhibit increased glucose serum levels
• however, all of streptozotocin-treated mice transplanted with islet cells from Prkdcscid/Prkdcscid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 positive human peripheral blood mononuclear cells exhibit euglycemia

immune system
• streptozotocin-treated mice transplanted with islet cells from Prkdcscid/Prkdcscid Tg(HLA-A2.1)1Enge Tg(B2M)55Hpl transgenic mice and HLA-A2 negative human peripheral blood mononuclear cells exhibit destruction of engrafted islet cells