Phenotypes associated with this allele

• Allele Symbol: Prdm1^tm1Clme
• Allele Name: targeted mutation 1, Kathryn Calame
• Allele ID: MGI:3605621
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Kras^tm4Tyj/Kras^+ Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Pdx1-cre)6Tuv/0 Trp53^tm2Tyj/Trp53^+	involves: 129 * C57BL/6NCrl * FVB/N	MGI:6296000
cn2	Cd19^tm1(cre)Cgn/Cd19^+ Prdm1^tm1Clme/Prdm1^tm1Clme	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:3606173
cn3	Il6^tm1Kopf/Il6^+ Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Itgax-cre)1-1Reiz/0	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CBA	MGI:5515639
cn4	Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Itgax-cre)1-1Reiz/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:5515634
cn5	Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Pdx1-cre)6Tuv/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:6295997

Genotype
MGI:6296000

cn1

• Allelic Composition: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Kras^tm4Tyj/Kras⁺; Prdm1^tm1Clme/Prdm1^tm1Clme; Tg(Pdx1-cre)6Tuv/0; Trp53^tm2Tyj/Trp53⁺
• Genetic Background: involves: 129 * C57BL/6NCrl * FVB/N

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

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:245611 )

• mice exhibit a similar overall pancreatic tumor burden as KPCT (Kras^tm4Tyj/Kras⁺ Trp53^tm2Tyj/Trp53⁺ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺) mice

• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice

• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells

• cancer cells exhibit a higher mitotic index than KPCT mice

increased pancreatic intraepithelial neoplasia incidence ( J:245611 )

• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice

mortality/aging

premature death ( J:245611 )

• mice exhibit a shorter survival than KPCT mice

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:245611 )

• mice exhibit a similar overall pancreatic tumor burden as KPCT (Kras^tm4Tyj/Kras⁺ Trp53^tm2Tyj/Trp53⁺ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺) mice

• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice

• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells

• cancer cells exhibit a higher mitotic index than KPCT mice

increased pancreatic intraepithelial neoplasia incidence ( J:245611 )

• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice

Genotype
MGI:3606173

cn2

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Prdm1^tm1Clme/Prdm1^tm1Clme
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

immune system

abnormal B cell differentiation ( J:101890 )

• following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice

• a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization

abnormal plasma cell differentiation ( J:101890 )

• the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants

abnormal memory B cell number ( J:101890 )

• pre-plasma memory B-cells are reduced by 75% in the spleen and 95% in the bone marrow, and CD138-B220+NP+ cells comprise the majority of memory B cells

abnormal plasma cell morphology ( J:101890 , J:114881 )

• antibody stimulating cell development is completely inhibited in cultures of stimulated B cells, however stimulation of B cells with LPS or LPS and IL-4 results in increased class switch recombination (J:114881)

decreased plasma cell number ( J:101890 )

• very few CD138+B220+/- plasma cells are seen at any time before or after immunization

• 5 days after re-challenge a 99% reduction in CD138+ B220+/- NP+ plasma cells is seen

increased spleen germinal center number ( J:101890 )

• more numerous germinal centers are seen after immunization

increased spleen germinal center size ( J:101890 )

• larger germinal centers are seen after immunization

decreased immunoglobulin level ( J:101890 )

• serum Ig levels are reduced in unimmunized mice

decreased IgG level ( J:101890 )

• in mice immunized with NP-Ficoll serum IgG1 and IgG2a levels are significantly lower in mutants compared to wild-type mice and mutant mice fail to secrete Ig in a recall response

decreased IgM level ( J:101890 )

• in mice immunized with NP-Ficoll serum IgM levels are significantly lower in mutants compared to wild-type mice and homozygous mice fail to secrete Ig in a recall response

hematopoietic system

abnormal B cell differentiation ( J:101890 )

• following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice

• a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization

abnormal plasma cell differentiation ( J:101890 )

• the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants

abnormal memory B cell number ( J:101890 )

• pre-plasma memory B-cells are reduced by 75% in the spleen and 95% in the bone marrow, and CD138-B220+NP+ cells comprise the majority of memory B cells

abnormal plasma cell morphology ( J:101890 , J:114881 )

• antibody stimulating cell development is completely inhibited in cultures of stimulated B cells, however stimulation of B cells with LPS or LPS and IL-4 results in increased class switch recombination (J:114881)

decreased plasma cell number ( J:101890 )

• very few CD138+B220+/- plasma cells are seen at any time before or after immunization

• 5 days after re-challenge a 99% reduction in CD138+ B220+/- NP+ plasma cells is seen

increased spleen germinal center number ( J:101890 )

• more numerous germinal centers are seen after immunization

increased spleen germinal center size ( J:101890 )

• larger germinal centers are seen after immunization

decreased immunoglobulin level ( J:101890 )

• serum Ig levels are reduced in unimmunized mice

decreased IgG level ( J:101890 )

• in mice immunized with NP-Ficoll serum IgG1 and IgG2a levels are significantly lower in mutants compared to wild-type mice and mutant mice fail to secrete Ig in a recall response

decreased IgM level ( J:101890 )

• in mice immunized with NP-Ficoll serum IgM levels are significantly lower in mutants compared to wild-type mice and homozygous mice fail to secrete Ig in a recall response

Genotype
MGI:5515639

cn3

• Allelic Composition: Il6^tm1Kopf/Il6⁺; Prdm1^tm1Clme/Prdm1^tm1Clme; Tg(Itgax-cre)1-1Reiz/0
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CBA

immune system

immune system phenotype ( J:178876 )

N • mice do not develop autoantibodies, they mount an antibody response indistinguishable from control mice to NP-CGG, dendritic cells express the same level of IL-6 as dendritic cells from control mice after LPS stimulation, and show normal levels of follicular T helper cells and germinal cells in the spleen

Genotype
MGI:5515634

cn4

• Allelic Composition: Prdm1^tm1Clme/Prdm1^tm1Clme; Tg(Itgax-cre)1-1Reiz/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

immune system

abnormal T follicular helper cell differentiation ( J:178876 )

♀ • generation of follicular T helper cells cells is enhanced when mutant dendritic cells are cultured with naive T cells from control mice in the presence of differentiation factors, indicating increased differentiation of these cells

increased germinal center B cell number ( J:178876 )

♀ • more spontaneous germinal center B cells

increased T follicular helper cell number ( J:178876 )

♀ • increase in the percentage and number of follicular T helper cells

increased spleen germinal center number ( J:178876 )

♀ • more germinal centers in the spleen

increased splenocyte number ( J:178876 )

♀ • total number of splenocytes are increased in females but not males

abnormal immune system physiology ( J:178876 )

♀ • enhanced immune response after NP-CGG immunization with an increased high-affinity anti-NP IgG response, an increase in the number of germinal center B cells, and an increase in the number of total germinal cells and antigen-specific germinal cells

abnormal germinal center B cell physiology ( J:178876 )

♀ • enhanced germinal center response in young mice

increased immunoglobulin level ( J:178876 )

♀ • total serum immunoglobulin levels are increased in females but not males

increased IgG level ( J:178876 )

♀ • kidney deposition of IgG in 10 month old females

abnormal CD4-positive, alpha-beta T cell physiology ( J:178876 )

♀ • increase in expression of ICOS in CD4+ T cells, indicating that mice have more activated CD4+ T cells than controls

increased interleukin-6 secretion ( J:178876 )

♀ • increase in production of IL-6 by splenic dendritic cells and by bone marrow derived dendritic cells after LPS stimulation in females but not males

increased autoantibody level ( J:178876 )

♀ • females, but not males, develop autoantibodies as early as 4-5 months of age, including anti-nuclear antibodies, anti-double stranded dNA, and anti-ENA5, which are all IgG

increased anti-nuclear antigen antibody level ( J:178876 )

♀

increased anti-double stranded DNA antibody level ( J:178876 )

♀ • IgG2b is the major isotype of anti-dsDNA antibodies

kidney inflammation ( J:178876 )

♀ • inflammatory infiltrates in 10 month old females

renal/urinary system

increased urine protein level ( J:178876 )

♀ • proteinuria in 10 month old females

kidney inflammation ( J:178876 )

♀ • inflammatory infiltrates in 10 month old females

abnormal kidney morphology ( J:178876 )

♀ • kidney deposition of IgG in 10 month old females

abnormal mesangial cell morphology ( J:178876 )

♀ • mesangial cell proliferation in 10 month old females

hematopoietic system

abnormal T follicular helper cell differentiation ( J:178876 )

♀ • generation of follicular T helper cells cells is enhanced when mutant dendritic cells are cultured with naive T cells from control mice in the presence of differentiation factors, indicating increased differentiation of these cells

increased germinal center B cell number ( J:178876 )

♀ • more spontaneous germinal center B cells

increased T follicular helper cell number ( J:178876 )

♀ • increase in the percentage and number of follicular T helper cells

increased spleen germinal center number ( J:178876 )

♀ • more germinal centers in the spleen

increased splenocyte number ( J:178876 )

♀ • total number of splenocytes are increased in females but not males

abnormal germinal center B cell physiology ( J:178876 )

♀ • enhanced germinal center response in young mice

increased immunoglobulin level ( J:178876 )

♀ • total serum immunoglobulin levels are increased in females but not males

increased IgG level ( J:178876 )

♀ • kidney deposition of IgG in 10 month old females

abnormal CD4-positive, alpha-beta T cell physiology ( J:178876 )

♀ • increase in expression of ICOS in CD4+ T cells, indicating that mice have more activated CD4+ T cells than controls

homeostasis/metabolism

increased urine protein level ( J:178876 )

♀ • proteinuria in 10 month old females

cellular

abnormal mesangial cell morphology ( J:178876 )

♀ • mesangial cell proliferation in 10 month old females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:178876

Genotype
MGI:6295997

cn5

• Allelic Composition: Prdm1^tm1Clme/Prdm1^tm1Clme; Tg(Pdx1-cre)6Tuv/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:245611 )

N • mice are viable and pancreata show no histologic changes