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Allele Symbol Allele Name Allele ID |
Rag2tm1Fwa targeted mutation 1, Frederick W Alt MGI:1858556 |
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| Summary |
76 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• migration of proliferated intestinal epithelial cells (IEC) toward the top of the villi, the number of proliferating IECs, and MHC class II expression on IECs are augmented in mutants compared to wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice survive infection with M. tuberculosis for the period of observation (day 50), whereas Ifng-null animals all succumb rapidly to infection
• neutralization of Ifng in infected mice abolishes the resistance to infection displayed by untreated mice
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• in this animal model of colitis, less severe pathological injury is observed in mice receiving Tg(CD2-Caecam1*4L)1Rsb T cell transfer
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• in this animal model of colitis, less severe pathological injury is observed in mice receiving Tg(CD2-Caecam1*4L)1Rsb T cell transfer
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• thymocyte number is reduced to 1-3 x 106 cells compared to 200-300 x 106 cells in wild-type mice
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• colonic lamina propria lymphocytes (LPL) produce less Ifng and IL-2 in recipients of Tg(CD2-Caecam1*4L)1Rsb T cells
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• in anti-Ifng treated mice, upregulation of Nos2 production by macrophages is abolished after M. tuberculosis infection relative to untreated Rag2-null mice wherease YM-1 and L-arginase 1 expression are elevated 60- and 3000-fold compared to untreated mutants
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• chemokines KC and MIP-2 are increased in NK cells in infected lungs of anti-Ifng treated mice
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• incubation of Rag2-null splenocytes with mycobacteria (M. tuberculosis) induces high levels of interferon gamma; this induction is increased at higher multiplicities of infection (MOI)
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• at 28 days p.i., lungs display a few small foci with limited mononuclear infiltration
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• mice survive infection with M. tuberculosis for the period of observation (day 50), whereas Ifng-null animals all succumb rapidly to infection
• neutralization of Ifng in infected mice abolishes the resistance to infection displayed by untreated mice
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• in lungs and spleens of M. tuberculosis-infected mice at 28 days post-infection (p.i.), bacterial loads are higher than in infected wild-type mice
• neutralization of Ifng in infected mice results in 0.5-1.0 log higher bacterial burdens in lungs and spleens than in untreated Rag2-null mice
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• in a mouse model of colitis, recipients of Tg(CD2-Caecam1*4L)1Rsb splenic T cells display less severe wasting than recipients of wild-type splenic T cells`
• this is associated with less severe macro- and microscopic colitis
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• thymocyte number is reduced to 1-3 x 106 cells compared to 200-300 x 106 cells in wild-type mice
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• colonic lamina propria lymphocytes (LPL) produce less Ifng and IL-2 in recipients of Tg(CD2-Caecam1*4L)1Rsb T cells
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• in anti-Ifng treated mice, upregulation of Nos2 production by macrophages is abolished after M. tuberculosis infection relative to untreated Rag2-null mice wherease YM-1 and L-arginase 1 expression are elevated 60- and 3000-fold compared to untreated mutants
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• at 28 days p.i., lungs display a few small foci with limited mononuclear infiltration
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• thymocyte number is reduced to 1-3 x 106 cells compared to 200-300 x 106 cells in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thymus contains few CD44+,CD25-,CD117++ double negative (DN1) cells and CD44+,CD25+ double negative (DN2) cells, representing 7.5% of that in a control mouse
(J:81133)
• the number of DN1 and DN2 cells is decreased
(J:91542)
• the population of DN1 cells remaining is enriched for proliferating CD117+ cells
(J:91542)
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• the number of DN3 cells is increased 2 fold
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• a complete block in T cell development at the double negative 3 stage is seen
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• proportion of CD19+, B220+ B cells in the neonatal thymus is extremely low
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• contact hypersensitivity is abolished compared to in wild-type mice
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• mice show no sign of lesion development for up to 12 to 14 weeks after infection; after 20 weeks, all lesions remain small
• mice reconstituted with 1x10 7 CD4+ T cells develop smaller lesions containing 100-fold less parasites than wild-type or mutants reconstituted with 1.5x10 7 CD4+ T cells
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• when given 10-20 mg/kg indomethacin, mice develop small nonhemorrhagic lesions in the jejunum, similar to controls in severity
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• when given 10-20 mg/kg indomethacin, mice develop extensive hemorrhagic lesions of the gastric mucosa, similar to controls in severity
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• thymus contains few CD44+,CD25-,CD117++ double negative (DN1) cells and CD44+,CD25+ double negative (DN2) cells, representing 7.5% of that in a control mouse
(J:81133)
• the number of DN1 and DN2 cells is decreased
(J:91542)
• the population of DN1 cells remaining is enriched for proliferating CD117+ cells
(J:91542)
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• the number of DN3 cells is increased 2 fold
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• a complete block in T cell development at the double negative 3 stage is seen
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• proportion of CD19+, B220+ B cells in the neonatal thymus is extremely low
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• smaller in size than wild-type or heterozygous littermates when maintained in nonbarrier facilities
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• decrease in cellularity of the thymus
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• inability to initiate V(D)J recombination
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• B cell development is arrested at the point at which Ig gene rearrangement is initiated
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• inability to initiate V(D)J recombination
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• absent double positive cells in thymus
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• majority of thymocytes are arrested at an early precursor stage of differentiation
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• spleens contain increased numbers of granulocytes
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• absent mature B lymphocytes; only very immature lymphoid cells are seen in primary lymphoid organs
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• spleens contain increased numbers of macrophages
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• absence of mature T cells
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• absence of single positive cells in the thymus, although spleen contains a small population of CD4+ T cells
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• absence of single positive cells in the thymus, although spleen contains a small population of CD8+ T cells
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• spleens contain increased numbers of macrophages and granulocytes
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• spleens contain 5-10 times fewer cells than control spleens
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• absent IgM
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• mutants have a higher level of splenic natural killer activity than controls
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• mutants develop infections when maintained in nonbarrier facilities for several months
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• decrease in cellularity of the thymus
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• inability to initiate V(D)J recombination
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• B cell development is arrested at the point at which Ig gene rearrangement is initiated
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• inability to initiate V(D)J recombination
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• absent double positive cells in thymus
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• majority of thymocytes are arrested at an early precursor stage of differentiation
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• spleens contain increased numbers of granulocytes
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• absent mature B lymphocytes; only very immature lymphoid cells are seen in primary lymphoid organs
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• spleens contain increased numbers of macrophages
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• absence of mature T cells
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• absence of single positive cells in the thymus, although spleen contains a small population of CD4+ T cells
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• absence of single positive cells in the thymus, although spleen contains a small population of CD8+ T cells
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• spleens contain increased numbers of macrophages and granulocytes
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• spleens contain 5-10 times fewer cells than control spleens
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• absent IgM
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• mutants have a higher level of splenic natural killer activity than controls
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• decrease in cellularity of the thymus
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, Nk cell-positive | DOID:0090013 |
OMIM:601457 |
J:1935 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thymus cellularity is reduced by a third
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• development is impaired at the pro-B cell stage
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• 4-fold decrease in DN cells
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• 4-fold reduction in the number of gamma-delta T cells in the thymus
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• T cell development is partially blocked at the CD25+ CD44- (DNIII) stage
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• one-third reduction in the number of immature B cells found in bone marrow
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• increase in pro-B cell
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• spleen and lymph nodes have half the number of mature B cells as wild-type controls
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• one-third reduction in the number of pre-B cells found in bone marrow
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• thymus cellularity is reduced by a third
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• development is impaired at the pro-B cell stage
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• 4-fold decrease in DN cells
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• 4-fold reduction in the number of gamma-delta T cells in the thymus
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• T cell development is partially blocked at the CD25+ CD44- (DNIII) stage
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• one-third reduction in the number of immature B cells found in bone marrow
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• increase in pro-B cell
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• spleen and lymph nodes have half the number of mature B cells as wild-type controls
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• one-third reduction in the number of pre-B cells found in bone marrow
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• thymus cellularity is reduced by a third
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• three fold fewer pro-B cells
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• three fold fewer pro-B cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• despite increased double positive T cell production stimulated by anti-CD3epsilon treatment, mice produce fewer double positive T cells compared to similarly treated Rag2tm1Fwa homozygotes
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• despite increased double positive T cell production stimulated by anti-CD3epsilon treatment, mice produce fewer double positive T cells compared to similarly treated Rag2tm1Fwa homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• with CCl4 treatment, adenocre administration, and GdCl3 10 days post-cre treatment to reduce Kuppfler cells, a major reduction in hepatocyte DNA synthesis is observed (1.8-2-fold reduction in BrdU incorporation)
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• 6-8 week-old mice treated with adeno-cre to delete HGF receiving CCl4 to induce liver injury and GdCl3 either 24 hours prior to and with cre treatment or 10 days post-cre treatment to reduce Kuppfler cell numbers show significantly reduced liver regeneration capacity
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• with CCl4 treatment, adenocre administration, and GdCl3 10 days post-cre treatment to reduce Kuppfler cells, a major reduction in hepatocyte DNA synthesis is observed (1.8-2-fold reduction in BrdU incorporation)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice succumb to disease at 12-16 weeks of age
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• marker analysis indicates impaired keratinocyte differentiation
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• mice develop mild skin dermatitis
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• mice develop mild skin dermatitis
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• marker analysis indicates impaired keratinocyte differentiation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
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• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
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• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
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• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
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• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• T cells expressing the transgenic MHC class II-restricted TCR show diversion from the CD4+ lineage to the CD8+ lineage
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• T cells expressing the transgenic MHC class II-restricted TCR show diversion from the CD4+ lineage to the CD8+ lineage
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• mice lack all B cells
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• mice lack all NK cells
• NK cells that are transferred into these mice are able to proliferate with a lifespan of about 10 days
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• mice lack all T cells
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• mice lack all B cells
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• mice lack all NK cells
• NK cells that are transferred into these mice are able to proliferate with a lifespan of about 10 days
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• mice lack all T cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice injected with A549 cells exhibit a reduction in the number of tumors that develop compared with similarly treated wild-type mice
• however, A549 cell tumor growth is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 1.8 fold increase in clonotype positive cells in the thymus of female but not male mice
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• 3 fold increase in clonotype CD4 T cells in female but not male mice
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• 1.8 fold increase in clonotype positive cells in the thymus of female but not male mice
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• 3 fold increase in clonotype CD4 T cells in female but not male mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Ncr(NKp46)+ NK1.1+ NK cells are essentially absent
• however, the NKp46+CD127+ NK1.1- subset of intestinal natural killer cells is unaffected
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• Ncr(NKp46)+ NK1.1+ NK cells are essentially absent
• however, the NKp46+CD127+ NK1.1- subset of intestinal natural killer cells is unaffected
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• transcript analysis of double-negative thymocytes reveals a 10-fold drop in use of the Tcrd-V5 gene segment
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• transcript analysis of double-negative thymocytes reveals a 10-fold drop in use of the Tcrd-V5 gene segment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• body weight of mice treated with estradiol is reduced relative to that of untreated controls
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• in response to estradiol treatment
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• reduced total cholesterol in response to estradiol treatment
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• in response to estradiol treatment
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• decreased fatty streak lesions in the aortic root in response to estradiol treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Ncr(NKp46)+ NK1.1+ NK cells are essentially absent
• the NKp46+CD127+ NK1.1- subset of intestinal natural killer cells is also absent
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• there is no interleukin 22 (IL-22) secretion by colonic lamina propia cells isolated from mice infected with C. rodentium compared to controls that secrete detectable amounts of IL-22
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• mice are extremely susceptible to C. rodentium infection, with all mice showing dramatic weight loss and succumbing to infection by day 7
• controls (Rag2 knockouts, Rag2 and Il2rg double knockouts) are not susceptible to infection
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• Ncr(NKp46)+ NK1.1+ NK cells are essentially absent
• the NKp46+CD127+ NK1.1- subset of intestinal natural killer cells is also absent
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 2-fold less NK cells are found in the spleen 5 days after transfer into these recipient mice compared to control mice
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• 2-fold less NK cells are found in the spleen 5 days after transfer into these recipient mice compared to control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• body weight of mice treated with estradiol is reduced relative to that of untreated controls
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• in response to estradiol treatment
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• reduced total cholesterol in response to estradiol treatment
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• in response to estradiol treatment
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• increased fatty streak lesions in the aortic root in response to estradiol treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no double positive or single positive T cells are detected in triple mutants
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• no double positive or single positive T cells are detected in triple mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells
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• a high proportion of CD38+ CD8+ T cells appear activated in HIV-infected BLT transplanted mice
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• spleen and lymph nodes lack lymphocytes
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• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells
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• mice fail to develop peripheral lymph nodes
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• 54% of BLT transplanted mice inoculated intrarectally with HIV become infected with plasma viral titers peaking between 2 and 4 weeks
• 100% of transplanted mice inoculated intraperitoneally with HIV become infected
• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells
• a high proportion of CD8+ T cells appear activated in HIV-infected BLT transplanted mice
• infected mice produce HIV-specific antibodies and can mount HIV-specific T cell responses
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• mice are tolerized to xenotransplantation with human bone marrow, liver, thymus (BLT)
• mice average 1x106 human leukocytes/mL blood 12 weeks after transplantation and levels remain stable or improve through 21 weeks
• >80% of leukocytes in peripheral circulation are human
• transplanted mice have higher levels of multipotent bone marrow/hematopoietic stem cells than mice heterozygous for the Cd47tm1Fpl allele
• GVHD is not evident in mice 25 weeks post-transplantation
• human thymic organoids are highly vascularized
• large and small intestines of transplanted mice contain CD4+ and CD8+ human T cells
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• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells
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• a high proportion of CD38+ CD8+ T cells appear activated in HIV-infected BLT transplanted mice
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• spleen and lymph nodes lack lymphocytes
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• HIV-infected BLT transplanted mice exhibit a loss of CD4+ T cells and an increase in CD8+ T cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice fed chicken ovalbumin exhibit a reduced increase the number and frequency of regulatory T cells in the large intestine lamina propria comparted with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike Unc93b1tm1.1Kmiy homozygotes, mice do not exhibit premature death
|
| N |
• platelet counts are the same as in Rag2tm1Fwa homozygotes
• unlike in Unc93b1tm1.1Kmiy homozygotes, spleen size is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• colitis nor associated changes in intestinal architecture are not observed in these mice, suggesting mature lymphocytes propogate colitis in mice lacking expression of IL2
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• no anemia is observed in these animals
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall
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• are increased 3-10 fold in size as compared to control littermates
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• is rarely observed
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• loss of mucin is observed in goblet cells
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• crypt hyperplasia and unusual branching is observed
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• occasional occurrence among mice whom live past 9 weeks of age
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• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall
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• is rarely observed
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• occurs in mice 24 weeks of age
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• loss of mucin is observed in goblet cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 8 weeks
• 3- to 4-fold at 3 months
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• thymocyte development arrests at the DN3 stage unlike in wild-type mice
|
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• at 8 weeks
• 3- to 4-fold at 3 months
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• thymocyte development arrests at the DN3 stage unlike in wild-type mice
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• in reconstitution experiments, thymocyte numbers are increased and thymic reconstitution dependent on stromal cells is enhanced compared to when wild-type bone marrow is used
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• at 8 weeks
• 3- to 4-fold at 3 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased proportion of IFN-gamma-producing cells in draining lymph nodes after adoptive transfer nae T cells
|
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• increase in the percentage of IL-17-producing cells in culturing CD4+ T cells in vitro under Th17-polarizing conditions
• produce more than twice as many Th17 cells in draining lymph nodes after adoptive transfer naive T cells
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• decreased proportion of IFN-gamma-producing cells in draining lymph nodes after adoptive transfer nae T cells
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• increase in the percentage of IL-17-producing cells in culturing CD4+ T cells in vitro under Th17-polarizing conditions
• produce more than twice as many Th17 cells in draining lymph nodes after adoptive transfer naive T cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit the same clinical symptoms as in Dnajc11spc homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show no signs of T cell activation, lymphadenopathy, or splenomegaly over 32 weeks; T cells are naive, with no expression of activation markers
• primary response to antigen stimulation in vitro is similar to Rag1-null, Tg(DO11.10)10Dlo T cells
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• during secondary response to low-dose antigen stimulation in vitro, T cells show 2.2-3 fold higher proliferation compared to Rag2-null, Tg(Do11.10)10Dlo mice
• transferred T cells are resistant to tolerance induction in vivo in hosts after a tolerizing dose of ovalbumin peptide; in vivo expansion of T cells 4 and 7 days after treatment is 2.2- and 1.4-fold greater than Rag2-null, transgenic mice
• T cells given a tolerogenic stimulus proliferate and secrete Il-2 robustly upon restimulation in contrast to poor response in Rag2-null, Tg(DO11.10)10Dlo mice
• T cells given a tolerogenic stimulus do not exhibit a blockade after entering G1 phase of cell cycle, and readily enter S phase, while Ctla4-sufficient mutant cells do not progress past G1
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• during secondary response, on days 2 and 3, T cells show increased production of interferon gamma and Il-4 than transgenic, Rag2-null mice
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• during secondary response to low-dose antigen stimulation in vitro, T cells show 2.2-3 fold higher proliferation compared to Rag2-null, Tg(Do11.10)10Dlo mice
• transferred T cells are resistant to tolerance induction in vivo in hosts after a tolerizing dose of ovalbumin peptide; in vivo expansion of T cells 4 and 7 days after treatment is 2.2- and 1.4-fold greater than Rag2-null, transgenic mice
• T cells given a tolerogenic stimulus proliferate and secrete Il-2 robustly upon restimulation in contrast to poor response in Rag2-null, Tg(DO11.10)10Dlo mice
• T cells given a tolerogenic stimulus do not exhibit a blockade after entering G1 phase of cell cycle, and readily enter S phase, while Ctla4-sufficient mutant cells do not progress past G1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the osteoarthritic phenotype of Errfi1 targeted mutants is not rescued by disruption of Rag2 indicating that the acquired immune system is not required for the development of this phenotype
|
|
• the osteoarthritic phenotype of Errfi1 targeted mutants is not rescued by disruption of Rag2 indicating that the acquired immune system is not required for the development of this phenotype
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after injection with anti-CD3epsilon antibodies number of thymocytes increases 60-fold compared to Ccnd3-competent, Rag2 null animals
|
|
• after injection with anti-CD3epsilon antibodies number of thymocytes increases 60-fold compared to Ccnd3-competent, Rag2 null animals
|
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• after injection with anti-CD3epsilon antibodies number of thymocytes increases 60-fold compared to Ccnd3-competent, Rag2 null animals
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• chemokines KC and MIP-2 are increased in NK cells in infected lungs
|
|
• splenocytes produce minimal levels of Ifng in response to mycobacterial stimulation, in contrast to response of Rag2-null cells
|
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• at 28 days post-infection (p.i.), lungs display exacerbated pulmonary inflammatory pathology relative to Rag2-null animals; lesions contain significant numbers of granulocytes compared to Il2rg, Rag2-double null mice
|
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• mice succumb rapidly to infection compared to Rag2-null mice
• in lungs and spleens of M. tuberculosis-infected mice at 28 days post-infection (p.i.), bacterial loads are 0.5-1.0 log higher than in infected Rag2-null mice
|
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• at 28 days post-infection (p.i.), lungs display exacerbated pulmonary inflammatory pathology relative to Rag2-null animals; lesions contain significant numbers of granulocytes compared to Il2rg, Rag2-double null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• splenocytes produce minimal levels of Ifng in response to mycobacterial stimulation, in contrast to response of Rag2-null cells
|
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• mice have higher numbers of lesions than Il2b, Rag2-null mice, but size of inflammatory foci and percentage of lung space affected is lower but lesions contain similar numbers of neutrophils
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• mice display transiently increased resistance to infection by M. tuberculosis relative to Il12b, Rag2-double null mice which die about 3 days sooner
• pulmonary bacterial loads are slightly but significantly decreased compared to Il12b, Rag2-null mutants
|
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• mice have higher numbers of lesions than Il2b, Rag2-null mice, but size of inflammatory foci and percentage of lung space affected is lower but lesions contain similar numbers of neutrophils
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8 expression on T cells from female mice is lower compared to T cells from female mutant mice that have wild-type Cd8a alleles
|
|
• CD8 expression on T cells from female mice is lower compared to T cells from female mutant mice that have wild-type Cd8a alleles
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells from this mouse strain have a high affinity for male H-Y antigen and are sensitive to diphtheria toxin
• approximately 90% depletion of these T cells occurs upon diphtheria toxin injection into a host mouse strain carrying these cells
|
|
• T cells from this mouse strain have a high affinity for male H-Y antigen and are sensitive to diphtheria toxin
• approximately 90% depletion of these T cells occurs upon diphtheria toxin injection into a host mouse strain carrying these cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• positive but not negative selection is impaired as evidenced by the low number of anti-HY (male antigen) T cells found in female mice
|
|
• there is about a 2-fold drop peripheral CD4 T cells for female but not male mice compared to controls
|
|
• there is a decrease (greater than 2-fold) in CD4-single positive thymocytes that express the transgenic TCR in female mice
|
|
• there is about a 2-fold drop in lymph node cellularity for female but not male mice compared to controls
|
|
• positive but not negative selection is impaired as evidenced by the low number of anti-HY (male antigen) T cells found in female mice
|
|
• there is about a 2-fold drop peripheral CD4 T cells for female but not male mice compared to controls
|
|
• there is a decrease (greater than 2-fold) in CD4-single positive thymocytes that express the transgenic TCR in female mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymus cellularity is reduced by more than half in female but not male mice compared to controls
|
|
• positive but not negative selection of MHC-II restricted T cells is impaired as evidenced by the low number of anti-HY (male antigen) CD4+T cells found in female mice
• when mice were irradiated and then reconstituted with bone marrow from OT-II mice, very few CD4+ T cells are produced
• when mice were irradiated and then reconstituted with bone marrow from OT-I mice, CD8+ T cells are produced at normal numbers
|
|
• the number of double-positive thymocytes is less than half in female but not male mice compared to controls
|
|
• there is about a 10-fold drop peripheral CD4 T cells for female but not male mice compared to controls
|
|
• there is a large decrease (greater than 5-fold) in CD4-single positive thymocytes that express the transgenic TCR in female mice
• CD4-single positive thymocytes expressing high levels of the transgenic TCR are decreased to an even greater extent
|
|
• spleen cellularity is reduced by about half in female but not male mice compared to controls
|
|
• there is about a 10-fold drop in lymph node cellularity for female but not male mice compared to controls
|
|
• thymus cellularity is reduced by more than half in female but not male mice compared to controls
|
|
• positive but not negative selection of MHC-II restricted T cells is impaired as evidenced by the low number of anti-HY (male antigen) CD4+T cells found in female mice
• when mice were irradiated and then reconstituted with bone marrow from OT-II mice, very few CD4+ T cells are produced
• when mice were irradiated and then reconstituted with bone marrow from OT-I mice, CD8+ T cells are produced at normal numbers
|
|
• the number of double-positive thymocytes is less than half in female but not male mice compared to controls
|
|
• there is about a 10-fold drop peripheral CD4 T cells for female but not male mice compared to controls
|
|
• there is a large decrease (greater than 5-fold) in CD4-single positive thymocytes that express the transgenic TCR in female mice
• CD4-single positive thymocytes expressing high levels of the transgenic TCR are decreased to an even greater extent
|
|
• spleen cellularity is reduced by about half in female but not male mice compared to controls
|
|
• thymus cellularity is reduced by more than half in female but not male mice compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time at which half of the mutants are sacrificed or die due to illness is 165 days
|
|
• thymoma develops in 55% of mutants, a lower frequency than in Trp53 homozygous mice
|
|
• thymoma develops in 55% of mutants, a lower frequency than in Trp53 homozygous mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time at which half of the mutants are sacrificed or die due to illness is 180 days
|
|
• thymoma develops in 67% of mutants
• tumors arise more slowly or with longer latency than in mice homozygous for Rag2 and heterozygous for Trp53, with mutants living 9% longer than controls
|
|
• thymoma develops in 67% of mutants
• tumors arise more slowly or with longer latency than in mice homozygous for Rag2 and heterozygous for Trp53, with mutants living 9% longer than controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• animals succumb to M. tuberculosis within 30 days, showing same median survival time as Ifng-null mice while wild-type survive infection for entire period of observation
|
|
|
• cells do not produce any interferon gamma after incubation of splenocytes with mycobacteria
|
|
|
• at 28 days post-infection (p.i.), lungs display massive lesions occupying about 60% of lung space compared to lungs in Rag2-null mice
|
|
|
• mice are more susceptible to infection than Rag2-null single mutants and show similar survival time to Ifng-null mice
• in lungs and spleens of M. tuberculosis-infected mice at 28 days post-infection (p.i.), bacterial loads are >2 log higher than in infected wild-type mice
|
|
|
• at 28 days post-infection (p.i.), lungs display massive lesions occupying about 60% of lung space compared to lungs in Rag2-null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a severe reduction in the percentage of thymocytes at the DN1-3 stages
|
|
• double-positive T cells make up 95% of the cells in the thymus
|
|
• CD4+ T cells make up about 3% of the splenocyte population
|
|
• gamma-delta T cells are absent in these mice
|
|
• there is a severe reduction in the percentage of thymocytes at the DN1-3 stages
|
|
• double-positive T cells make up 95% of the cells in the thymus
|
|
• CD4+ T cells make up about 3% of the splenocyte population
|
|
• gamma-delta T cells are absent in these mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a reduction in the percentage of thymocytes at DN1 and DN2 stages while there is a large increase in thymocytes at DN3 and DN4
|
|
• CD4+ T cells make up less than 1% of the splenocyte population
|
|
• 99% of T cells in the spleen are CD8+ T cells
• 46% of thymocytes are single-positive CD8+ cells
|
|
• gamma-delta T cells are absent in these mice
|
|
• there is a reduction in the percentage of thymocytes at DN1 and DN2 stages while there is a large increase in thymocytes at DN3 and DN4
|
|
• CD4+ T cells make up less than 1% of the splenocyte population
|
|
• 99% of T cells in the spleen are CD8+ T cells
• 46% of thymocytes are single-positive CD8+ cells
|
|
• gamma-delta T cells are absent in these mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice develop intestinal tumors
|
|
|
• mice develop spontaneous mammary adenocarcinoma
|
|
|
• mice develop spontaneous mammary adenocarcinoma
|
|
|
• mice develop intestinal tumors
|
|
|
• mice develop spontaneous mammary adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD19 enriched bone marrow cells have decreased Imu transcripts and no mu0 transcripts are detectable
|
|
• CD19 enriched bone marrow cells have decreased Imu transcripts and no mu0 transcripts are detectable
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD19 enriched bone marrow cells have decreased Imu and mu0 transcripts
|
|
• CD19 enriched bone marrow cells have decreased Imu and mu0 transcripts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• despite developing spontaneous ulcerative colitis, mice exhibit normal stomachs and small intestines
|
|
• at 3.5 weeks, mice exhibit large epithelial discontinuities with a 4- to 5-fold increase in apoptosis of epithelial cells compared with wild-type or single homozygous mice
• however, treatment with anti-TNF-alpha antibodies normalizes the level of apoptosis
|
|
• mice exhibit crypt loss associated with the development of colitis
|
|
• mice exhibit anorectal prolapse unlike wild-type or single homozygous mice
|
|
• at 3.5 weeks, colonic epithelial barrier is 2-fold more permeable than in Rag2tm1Fwa homozygotes
• at 4 to 5 weeks, colonic epithelial barrier is increased 3-fold
• at 5 to 6 weeks, colonic epithelial barrier is increased 8.6-fold
|
|
• by 4 weeks, mice develop inflammation of the rectum and left colon unlike or single homozygous wild-type mice
|
|
• mice exhibit inflammatory infiltrate in the lamina propria, neutrophil infiltration of the crypt and surface epithelium, and epithelial injury with surface denudations and ulcerations associated with crypt loss and epithelial mucodepletion
• by 4 weeks of age, mice develop highly penetrant and severe colitis unlike wild-type or single homozygous mice that increases in severity over time
• at 8 weeks, mice exhibit marked inflammation and colonic thickening unlike Rag2tm1Fwa homozygotes
• however, treatment with anti-TNF-alpha antibodies, T regulatory cells, or broad spectrum antibiotics restores normal colon phenotype, and treatment with broad spectrum antibiotics prevents communication of colitis to offspring
• female mice cross-fostering wild-type mice and Rag2tm1Fwa homozygotes fail to establish normal resistance to colitis in cross-fostered pups and mice can transmit susceptibility to colitis to wild-type mice housemates
|
|
• by 4 weeks, mice develop inflammation of the rectum and left colon unlike or single homozygous wild-type mice
|
|
• mice exhibit inflammatory infiltrate in the lamina propria, neutrophil infiltration of the crypt and surface epithelium, and epithelial injury with surface denudations and ulcerations associated with crypt loss and epithelial mucodepletion
• by 4 weeks of age, mice develop highly penetrant and severe colitis unlike wild-type or single homozygous mice that increases in severity over time
• at 8 weeks, mice exhibit marked inflammation and colonic thickening unlike Rag2tm1Fwa homozygotes
• however, treatment with anti-TNF-alpha antibodies, T regulatory cells, or broad spectrum antibiotics restores normal colon phenotype, and treatment with broad spectrum antibiotics prevents communication of colitis to offspring
• female mice cross-fostering wild-type mice and Rag2tm1Fwa homozygotes fail to establish normal resistance to colitis in cross-fostered pups and mice can transmit susceptibility to colitis to wild-type mice housemates
|
|
• as early as 2 weeks, colonic dendritic cells produce more TNF-alpha than wild-type cells
• in culture, bone marrow-derived dendritic cells produce more TNF-alpha compared with wild-type cells
• however, treatment with T regulatory cells reduced TNF-alpha levels
|
|
• mice exhibit crypt loss associated with the development of colitis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ulcerative colitis | DOID:8577 | J:141481 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
• T cells require about 2 logs higher concentration of antigen for proliferation equivalent of wild-type T cells
|
|
• thymocytes proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
|
|
• lymph node T cells secrete significantly less IL-2 than wild-type T cells in response to irradiated spleen cells loaded with VSV8 antigen
|
|
• T cells proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
• T cells require about 2 logs higher concentration of antigen for proliferation equivalent of wild-type T cells
|
|
• thymocytes proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
|
|
• thymocytes proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
|
|
• T cells proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
• T cells require about 2 logs higher concentration of antigen for proliferation equivalent of wild-type T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• CD8+ T cells show no differences in prevalence, numbers, or TCR expression levels relative to Arts1-sufficient Tg(TcrLCMV)327Sdz mice (on Rag2-null background)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with tumor cells exhibit reduced lung tumor burden compared with similarly treated wild-type mice with reduced tumor size
|
|
• metastatic lung tumors in mice injected with tumors cells exhibit decreased staining for blood vessels compared with equivalent tumors in wild-type mice
|
|
• metastatic lung tumors in mice injected with tumors cells exhibit decreased size compared with tumors induced in similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• T cells exhibit similar levels of activation induced cell death as Rag2-, Ctla4-deficient, Tg (DO11.10)10Dlo T cells
• cells undergo tolerance induction in vivo in response to an immunizing or tolerizing stimulus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 96% of thymocytes are double positive
• the presence of the transgene rescues the block of T cell development that occurs at DN3 in Rag2tm1Fwa homozygotes
|
|
• despite the presence of double positive thymocytes, single positive T cells do not develop
|
|
• despite the presence of double positive thymocytes, single positive T cells do not develop
|
|
• 96% of thymocytes are double positive
• the presence of the transgene rescues the block of T cell development that occurs at DN3 in Rag2tm1Fwa homozygotes
|
|
• despite the presence of double positive thymocytes, single positive T cells do not develop
|
|
• despite the presence of double positive thymocytes, single positive T cells do not develop
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• an increase in double positive thymocytes results from arrested thymocyte development
|
|
• there is a complete block in CD4 single-positive thymocyte development
• the minor CD8 single-positive population in transgenic mice is also significantly affected
|
|
• an increase in double positive thymocytes results from arrested thymocyte development
|
|
• there is a complete block in CD4 single-positive thymocyte development
• the minor CD8 single-positive population in transgenic mice is also significantly affected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the arthritis observed in Il6sttm1Thir homozygotes is not observed in these mice demonstrating functional lymphocytes are essential for disease
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a skewing towards the CD-4 T cell subset in mice on a homozygote H2k/k background
• the ratio of T cell subsets in the thymus is skewed toward CD8 T cells on a heterozygote H2b/k background
|
|
• 55.9% of the double-positive thymocytes express the transgenic TCR
|
|
• 15% of total lymphocytes found in lymph nodes are CD4 T cells bearing the transgenic TCR
• CD4 T cells that express the transgenic TCR-beta chain also express low or high amounts of the TCR-alpha chain
• the CD4 T cells expressing the low amounts of transgenic TCR-alpha may also express endogenous TCR-alpha chains
|
|
• the number of CD4 T cells in the spleen and lymph nodes is severely reduced
|
|
• in vitro TCR stimulation leads to reduced expression of CD69 compared to T cells from mice transgenic for just the TCR
|
|
• CD4 T cells expressing the transgenic TCR proliferate in response to hen egg lysozyme
• proliferation occurs whether CD4 T cells are low or high expressers of the transgenic TCR-alpha chain
|
|
• there is a skewing towards the CD-4 T cell subset in mice on a homozygote H2k/k background
• the ratio of T cell subsets in the thymus is skewed toward CD8 T cells on a heterozygote H2b/k background
|
|
• 55.9% of the double-positive thymocytes express the transgenic TCR
|
|
• 15% of total lymphocytes found in lymph nodes are CD4 T cells bearing the transgenic TCR
• CD4 T cells that express the transgenic TCR-beta chain also express low or high amounts of the TCR-alpha chain
• the CD4 T cells expressing the low amounts of transgenic TCR-alpha may also express endogenous TCR-alpha chains
|
|
• the number of CD4 T cells in the spleen and lymph nodes is severely reduced
|
|
• in vitro TCR stimulation leads to reduced expression of CD69 compared to T cells from mice transgenic for just the TCR
|
|
• CD4 T cells expressing the transgenic TCR proliferate in response to hen egg lysozyme
• proliferation occurs whether CD4 T cells are low or high expressers of the transgenic TCR-alpha chain
|
|
• there is a skewing towards the CD-4 T cell subset in mice on a homozygote H2k/k background
• the ratio of T cell subsets in the thymus is skewed toward CD8 T cells on a heterozygote H2b/k background
|
|
• CD4 T cells expressing the transgenic TCR proliferate in response to hen egg lysozyme
• proliferation occurs whether CD4 T cells are low or high expressers of the transgenic TCR-alpha chain
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 54% of mice develop thyroiditis compared to 100% of mice carrying both transgenes on a Rag2+ background
|
|
• the absolute number of double-positive T cells is reduced 3- to 4- fold
|
|
• there is reduced surface expression of T cell receptor components compared to mice transgenic for just the TCR transgene
• T cells also express surface markers indicative of recently being activated (high CD44, low CD45RB)
|
|
• the number of CD4 T cells in the spleen and lymph nodes is severely reduced
• there are 25-fold fewer peripheral T cells present than in Rag2 null homozygotes carrying just the TCR transgene
|
|
• CD4 T cells have a greatly reduced capability to activate and help B cell antibody production in vivo
|
|
• in vitro TCR stimulation leads to greatly reduced expression of CD69 compared to T cells from mice transgenic for just the TCR
|
|
• CD4 T cells have a reduced proliferative response to hen egg lysozyme antigen compared to CD4 T cells from mice carrying just the TCR transgene
|
|
• 54% of mice develop thyroiditis compared to 100% of mice carrying both transgenes on a Rag2+ background
|
|
• the absolute number of double-positive T cells is reduced 3- to 4- fold
|
|
• there is reduced surface expression of T cell receptor components compared to mice transgenic for just the TCR transgene
• T cells also express surface markers indicative of recently being activated (high CD44, low CD45RB)
|
|
• the number of CD4 T cells in the spleen and lymph nodes is severely reduced
• there are 25-fold fewer peripheral T cells present than in Rag2 null homozygotes carrying just the TCR transgene
|
|
• CD4 T cells have a greatly reduced capability to activate and help B cell antibody production in vivo
|
|
• in vitro TCR stimulation leads to greatly reduced expression of CD69 compared to T cells from mice transgenic for just the TCR
|
|
• CD4 T cells have a reduced proliferative response to hen egg lysozyme antigen compared to CD4 T cells from mice carrying just the TCR transgene
|
|
• CD4 T cells have a reduced proliferative response to hen egg lysozyme antigen compared to CD4 T cells from mice carrying just the TCR transgene
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the phenotype is similar to mice that are homozygote only for the Wdr1rede allele indicating that the inflammatory lesions are not the result of T-cell or B-cell activity
|
|
• three week old mice have about 5-fold less platelets per liter of blood compared to wild-type littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following primary, but not secondary, Salmonella infection
|
|
• following primary, but not secondary, Salmonella infection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8 T cells proliferate when presented VSV8 peptide by antigen presenting cells
|
|
• the majority of T cells in the thymus are arrested at the double positive stage
• single positive CD4 positive T cells are absent in the thymus
• there is a reduced percentage of single positive CD8 positive T cells
• however, the TCR transgene rescues the arrestment of T cells in the double negative stage that occurs in Rag2 deficient background
• injection of the VSV8 antigen leads to rapid apoptosis and depletion of double-positive thymocytes with a 3-6 fold drop in total number of thymocytes
|
|
• there are almost 10-fold less CD4 T cells in the spleen
|
|
• there are about 4-fold more CD8 T cells in the spleen
|
|
• CD8 positive T cells exhibit increased cytotoxicity towards cells loaded with VSV8 peptide
|
|
• CD8 T cells proliferate when presented VSV8 peptide by antigen presenting cells
|
|
• the majority of T cells in the thymus are arrested at the double positive stage
• single positive CD4 positive T cells are absent in the thymus
• there is a reduced percentage of single positive CD8 positive T cells
• however, the TCR transgene rescues the arrestment of T cells in the double negative stage that occurs in Rag2 deficient background
• injection of the VSV8 antigen leads to rapid apoptosis and depletion of double-positive thymocytes with a 3-6 fold drop in total number of thymocytes
|
|
• there are almost 10-fold less CD4 T cells in the spleen
|
|
• there are about 4-fold more CD8 T cells in the spleen
|
|
• CD8 positive T cells exhibit increased cytotoxicity towards cells loaded with VSV8 peptide
|
|
• CD8 T cells proliferate when presented VSV8 peptide by antigen presenting cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the majority of T cells in the thymus are arrested at the double positive stage
• single positive T cells are virtually absent
• however, the TCR transgene rescues the arrestment of T cells in the double negative stage that occurs in Rag2 deficient background
|
|
• mature CD4 T cells are severely reduced in the spleen
|
|
• mature CD8 T cells are virtually absent in the spleen
|
|
• the majority of T cells in the thymus are arrested at the double positive stage
• single positive T cells are virtually absent
• however, the TCR transgene rescues the arrestment of T cells in the double negative stage that occurs in Rag2 deficient background
|
|
• mature CD4 T cells are severely reduced in the spleen
|
|
• mature CD8 T cells are virtually absent in the spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 100-fold less NK cells are found in the spleen 5 days after transfer into these recipient mice compared to control mice
• the remaining NK cells have not proliferated within the first 3 days of transfer
• NK cells isolated from Tg(BCL2)25Wehi have a 2.5 fold higher survival rate 5 days after transfer into these recipient mice
|
|
• 100-fold less NK cells are found in the spleen 5 days after transfer into these recipient mice compared to control mice
• the remaining NK cells have not proliferated within the first 3 days of transfer
• NK cells isolated from Tg(BCL2)25Wehi have a 2.5 fold higher survival rate 5 days after transfer into these recipient mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 15% weight loss after treatment with 2.5% Sodium Dextran Sulfate (DSS) for 5 days
• fail to recover until 10 days after treatment
• IL22 treatment protects against weight loss
|
|
• increased crypt loss and epithelial damage after treatment with 2.5% DSS for 5 days
• IL22 treatment protects against crypt loss
|
|
• short colon after treatment with 2.5% DSS for 5 days
• IL22 treatment protects against colon shortening
|
|
• reduced expression of IL22 after DSS treatment
|
|
• reduced expression after DSS treatment
|
|
• reduced expression of IL22 after DSS treatment
|
|
• increased crypt loss and epithelial damage after treatment with 2.5% DSS for 5 days
• IL22 treatment protects against crypt loss
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymic cellularity is ~2-fold higher than in Rag2-sufficient transgenic mice
|
|
• rate of CD4+ T cell development is delayed by ~1 day relative to transgenic Rag2-sufficient animals
|
|
• accumulation of CD4+CD8+ thymocytes is observed
|
|
• CD4 single-positive thymocytes were reduced by >50% compared to Rag2-wild-type transgenic animals
|
|
• thymic cellularity is ~2-fold higher than in Rag2-sufficient transgenic mice
|
|
• rate of CD4+ T cell development is delayed by ~1 day relative to transgenic Rag2-sufficient animals
|
|
• accumulation of CD4+CD8+ thymocytes is observed
|
|
• CD4 single-positive thymocytes were reduced by >50% compared to Rag2-wild-type transgenic animals
|
|
• thymic cellularity is ~2-fold higher than in Rag2-sufficient transgenic mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit an abnormal skin phenotype similar to that observed in Tg(KRT14-Il1f5)1Hblu mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time at which half of the mutants are sacrificed or die due to illness is 167 days
|
|
• 83% incidence of thymoma
• tumors arise more slowly or with longer latency than in single hemizygous Tg(LPV-TAg1135)11Tvd mice, with mutants living 14% longer than controls
|
|
• 83% incidence of thymoma
• tumors arise more slowly or with longer latency than in single hemizygous Tg(LPV-TAg1135)11Tvd mice, with mutants living 14% longer than controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8 single-positive thymocytes are reduced in female mice compared to transgenic controls
|
|
• CD8 single-positive thymocytes are reduced in female mice compared to transgenic controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time at which half of the mutants are sacrificed or die due to illness is 146 days
|
|
• 100% incidence of thymoma
|
|
• 100% incidence of thymoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 to 30% DP thymocytes appear allowing some DN cells to progress to the DP state, which is fewer than in wild-type mice but more than in Rag2 null mice
|
|
• 4 to 30% DP thymocytes appear allowing some DN cells to progress to the DP state, which is fewer than in wild-type mice but more than in Rag2 null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8 expression is reduced by 80% in male mice compared to female mice
• CD8 expression on T cells from male mice did not change when cultured in the presence of IL-7
|
|
• CD8 T cells from male mice are refractory to IL-7 signaling as assessed by decreased CD8 expression, increased IL-7 receptor alpha expression, and decreased Stat5 phosphorylation
• defects can be rescued in vitro by limiting cell to cell contact or in vivo by crossing with mice that express MHC alleles that do not present the HY antigen
|
|
• female T cells respond to 10- to 100- fold less HY antigen than transgenic male T cells do
|
|
• CD8 expression is reduced by 80% in male mice compared to female mice
• CD8 expression on T cells from male mice did not change when cultured in the presence of IL-7
|
|
• CD8 T cells from male mice are refractory to IL-7 signaling as assessed by decreased CD8 expression, increased IL-7 receptor alpha expression, and decreased Stat5 phosphorylation
• defects can be rescued in vitro by limiting cell to cell contact or in vivo by crossing with mice that express MHC alleles that do not present the HY antigen
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• female T cells respond to 10- to 100- fold less HY antigen than transgenic male T cells do
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thymocyte number is only about 5-15 x 106 cells at 4-5 weeks of age compared to 200-300 x 106 cells in wild-type mice
• however, a gradual increase in the number of thymocytes occurs with cell numbers similar to wild-type by 8-9 weeks of age
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• thymocyte number is only about 5-15 x 106 cells at 4-5 weeks of age compared to 200-300 x 106 cells in wild-type mice
• however, a gradual increase in the number of thymocytes occurs with cell numbers similar to wild-type by 8-9 weeks of age
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• thymocyte number is only about 5-15 x 106 cells at 4-5 weeks of age compared to 200-300 x 106 cells in wild-type mice
• however, a gradual increase in the number of thymocytes occurs with cell numbers similar to wild-type by 8-9 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop thymic tumors consisting of cells of the double-positive stage of T-cell development
• development of tumors is delayed compared to single Tg(Cd4-NPM/ALK)N1Ingh transgenic mice
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• cortical thymic lymphoma
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• mice develop thymic tumors consisting of cells of the double-positive stage of T-cell development
• development of tumors is delayed compared to single Tg(Cd4-NPM/ALK)N1Ingh transgenic mice
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• cortical thymic lymphoma
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice do not develop lymphoid tumors, but present after a long latency with gastrointestinal stromal tumors
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• mice present after a long latency with hepatocellular carcinomas and sarcomas
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• mice present after a long latency with hepatocellular carcinomas and sarcomas
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• mice do not develop lymphoid tumors, but present after a long latency with gastrointestinal stromal tumors
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• mice present after a long latency with hepatocellular carcinomas and sarcomas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no monocyte memory response to BALB/c allograft 7 or 28 days after priming with irradiated BALB/c splenocytes
• normal primary response (primary dendritic cell and macrophage functions) to BALB/c allograft after priming with irradiated BALB/c splenocytes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• females develop diabetes at lower frequencies and later ages than wild-type Rag2 NOD transgenics
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/09/2024 MGI 6.23 |
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