Phenotypes associated with this allele

• Allele Symbol: Spi1^tm1.3Dgt
• Allele Name: targeted mutation 1.3, Daniel G Tenen
• Allele ID: MGI:3619530
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spi1^tm1.3Dgt/Spi1^tm1.3Dgt	involves: 129 * BALB/c * C57BL/6	MGI:3714968
hm2	Spi1^tm1.3Dgt/Spi1^tm1.3Dgt	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6	MGI:3620368

Genotype
MGI:3714968

hm1

• Allelic Composition: Spi1^tm1.3Dgt/Spi1^tm1.3Dgt
• Genetic Background: involves: 129 * BALB/c * C57BL/6

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

mortality/aging

premature death ( J:90331 )

• mice are moribund or die by 3 to 8 months from fatal, aggressive neoplastic disease

neoplasm

increased T cell derived lymphoma incidence ( J:90331 )

• T cell lymphomas accompany myeloid leukemia and was the dominant disease in 2 mice

increased leukemia incidence ( J:90331 )

• mice develop fatal, aggressive neoplastic disease similar to AML (acute myelogenous leukemia)

immune system

increased T cell derived lymphoma incidence ( J:90331 )

• T cell lymphomas accompany myeloid leukemia and was the dominant disease in 2 mice

increased neutrophil cell number ( J:90331 )

• at 2 to 3 months of age, neutrophil numbers are increased relative to wild-type mice

decreased B cell number ( J:90331 )

• mice have fewer B lymphoid cells

abnormal spleen morphology ( J:90331 )

• abnormal architecture due to expansion of myeloid cells

enlarged spleen ( J:90331 )

• spleen is 1.5 to 2 times bigger than in wild-type mice

increased spleen weight ( J:90331 )

• leukemic mice spleens weigh 600 to 1,600mg compared to 80 to 150mg in wild-type mice

spleen hyperplasia ( J:90331 )

• due to expansion of myeloid cells

liver/biliary system

abnormal liver morphology ( J:90331 )

• abnormal architecture due to expansion of myeloid cells

increased liver weight ( J:90331 )

• leukemic mice livers weigh 3.0 to 7.2g compared to 1 to 1.5g in wild-type mice

liver hyperplasia ( J:90331 )

• due to expansion of myeloid cells

cellular

abnormal chromosome number ( J:90331 )

• trisomy 15 is common in mice with T cell lymphomas

hematopoietic system

increased T cell derived lymphoma incidence ( J:90331 )

• T cell lymphomas accompany myeloid leukemia and was the dominant disease in 2 mice

abnormal definitive hematopoiesis ( J:90331 )

• moribund mice accumulate immature myeloid cells in bone marrow and spleen

abnormal proerythroblast morphology ( J:90331 )

• mice have fewer erythroid cells

increased neutrophil cell number ( J:90331 )

• at 2 to 3 months of age, neutrophil numbers are increased relative to wild-type mice

decreased B cell number ( J:90331 )

• mice have fewer B lymphoid cells

abnormal spleen morphology ( J:90331 )

• abnormal architecture due to expansion of myeloid cells

enlarged spleen ( J:90331 )

• spleen is 1.5 to 2 times bigger than in wild-type mice

increased spleen weight ( J:90331 )

• leukemic mice spleens weigh 600 to 1,600mg compared to 80 to 150mg in wild-type mice

spleen hyperplasia ( J:90331 )

• due to expansion of myeloid cells

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:90331 )

• T cell lymphomas accompany myeloid leukemia and was the dominant disease in 2 mice

growth/size/body

increased liver weight ( J:90331 )

• leukemic mice livers weigh 3.0 to 7.2g compared to 1 to 1.5g in wild-type mice

liver hyperplasia ( J:90331 )

• due to expansion of myeloid cells

enlarged spleen ( J:90331 )

• spleen is 1.5 to 2 times bigger than in wild-type mice

increased spleen weight ( J:90331 )

• leukemic mice spleens weigh 600 to 1,600mg compared to 80 to 150mg in wild-type mice

spleen hyperplasia ( J:90331 )

• due to expansion of myeloid cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:90331

Genotype
MGI:3620368

hm2

• Allelic Composition: Spi1^tm1.3Dgt/Spi1^tm1.3Dgt
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6

mortality/aging

premature death ( J:106040 )

• > 90% of mice homozygous for this mutation die between 3 and 13 months of age

neoplasm

increased T cell derived lymphoma incidence ( J:106040 )

• in 40% of mice with thymic lymphoma, lymphoma cells are present in the periphery where they greatly elevate peripheral blood lymphocyte numbers, form spleen and/or lymph node tumors, and invade nonhematopoietic organs

• T-cell lymphoma cells of homozygous mutant mice vary in their expression of CD4 and CD8 and are CD3^dim

• lymphoma cells of mutant mice express terminal deoxynucleotide transferase, a characteristic of immature T lymphoblast cells

• the lymphoma cells, unlike ordinary T-cell progenitor cells in these mice, express only low levels of PU.1/SFPI1

• analysis of the TCR-beta variable-region isotype of T-cell lymphoma cells from lymph node tumors indicates they are clonally derived

• a characteristic pattern of promoter hypermethylation is detected by RLGS analysis in T-cell lymphomas (but not in myeloid tumors) of homozygous mutant mice

• hypermethylation and transcriptional downregulation of the inhibitor of DNA binding 4 (Id4) tumor suppressor gene is characteristic of T-cell lymphomas, but not of myeloid tumors, of homozygous mutant mice

• T-cell lymphomas of these mice exhibit a characteristic pattern of promoter hypermethylation that is not shared by myeloid tumors in the same mice; inhibitor of DNA binding 4 (Id4, aka Idb4) is reproducibly hypermethylated and downregulated in these but not AML

• injection of lymphoma cells transmits the phenoytpe to NOD.CB17-Prkdc^scid mice, causing death within 3-6 weeks

increased leukemia incidence ( J:106040 )

• between 6 and 12 months of age, 29.0% of homozygous mice develop acute myeloid leukemia (AML)

immune system

small thymus ( J:106040 )

increased T cell derived lymphoma incidence ( J:106040 )

• in 40% of mice with thymic lymphoma, lymphoma cells are present in the periphery where they greatly elevate peripheral blood lymphocyte numbers, form spleen and/or lymph node tumors, and invade nonhematopoietic organs

• T-cell lymphoma cells of homozygous mutant mice vary in their expression of CD4 and CD8 and are CD3^dim

• lymphoma cells of mutant mice express terminal deoxynucleotide transferase, a characteristic of immature T lymphoblast cells

• the lymphoma cells, unlike ordinary T-cell progenitor cells in these mice, express only low levels of PU.1/SFPI1

• analysis of the TCR-beta variable-region isotype of T-cell lymphoma cells from lymph node tumors indicates they are clonally derived

• a characteristic pattern of promoter hypermethylation is detected by RLGS analysis in T-cell lymphomas (but not in myeloid tumors) of homozygous mutant mice

• hypermethylation and transcriptional downregulation of the inhibitor of DNA binding 4 (Id4) tumor suppressor gene is characteristic of T-cell lymphomas, but not of myeloid tumors, of homozygous mutant mice

• T-cell lymphomas of these mice exhibit a characteristic pattern of promoter hypermethylation that is not shared by myeloid tumors in the same mice; inhibitor of DNA binding 4 (Id4, aka Idb4) is reproducibly hypermethylated and downregulated in these but not AML

• injection of lymphoma cells transmits the phenoytpe to NOD.CB17-Prkdc^scid mice, causing death within 3-6 weeks

decreased pro-B cell number ( J:106040 )

• numbers of bone marrow pro-B cells (Lin^-IgM^-B220⁺CD43⁺) are greatly reduced

arrested B cell differentiation ( J:106040 )

• B cell differentiation is blocked before the pro-B cell stage in mutant mice, as numbers of bone marrow pro-B cells (Lin^-IgM^-B220⁺CD43⁺) and pre-B cells (Lin^-IgM^-B220⁺CD43^-) are greatly reduced

abnormal double-negative T cell morphology ( J:106040 )

• SFPI1/PU.1 is expressed at higher levels in mutant than in wild-type ETPs and DN1-DN3 thymocytes, but is turned off in both mutant and wild-type CD4⁺CD8⁺ (double positive, DP) thymocytes

decreased granulocyte number ( J:106040 )

• proportion of myeloid cells (Mac1^lowIgm^-) in the peritoneum diminishes over time

decreased mature B cell number ( J:106040 )

• mature B cell numbers are greatly reduced in bone marrow, spleen and liver of homozygous mutant mice

decreased B-1a cell number ( J:106040 )

• the intraperitoneal B1 cell population is skewed toward B1b cells (CD5^-), with concomitant reduction of the proportion of B1a cells (CD5⁺) from the 30-40% seen in wild-type mice to ~10-20% in homozygous mutants

decreased pre-B cell number ( J:106040 )

• numbers of bone marrow pre-B cells (Lin^-IgM^-B220⁺CD43^-) are greatly reduced

abnormal T cell subpopulation ratio ( J:106040 )

• the proportion of immature, CD4^-CD8^- (double negative, DN) thymocytes is elevated

• within the DN thymocyte population, the proportions of early, DN1-DN2 stage thymocytes are elevated, while later, DN3-DN4 stage thymocyte percentages are reduced

• mutant thymi contain elevated numbers of the earliest T cell lineage-restricted progenitor cells (ETPs, CD3^-CD4^-CD8^-Kit^bright), but reduced numbers of proT and preT cells

decreased T cell number ( J:106040 )

• numbers of mature CD4⁺ and CD8⁺ T cells in the periphery are slightly reduced in mutant mice

decreased thymocyte number ( J:106040 )

• thymi of mutant mice contain 3.4-fold fewer thymocytes than those of wild-type mice

increased lymphocyte cell number ( J:106040 )

• intraperitoneal lymphocyte numbers in mutant mice increase progressively with age, to greater than 3-fold wild-type numbers by 4-8 months

increased B-1 B cell number ( J:106040 )

• the percentage of physically and functionally normal B1 cells (Mac1^lowIgM^highCD43⁺B7.1⁺CD23^-CD19⁺B220^low) in the peritoneum increases with time

• B1 cells account for up to 43% of peripheral blood lymphocytes in older mutant mice, although they are not present in blood of wild-type mice

• Southern blot analysis of peritoneal lymphocytes for IghD-J rearrangements found evidence of clonal B1 cell proliferation in one mutant mouse of 6 studied at ages 6-8 mo

increased B-1b cell number ( J:106040 )

• the intraperitoneal B1 cell population is skewed toward B1b cells (CD5^-), with concomitant reduction of the proportion of B1a cells (CD5⁺) from the 30-40% seen in wild-type mice to ~10-20% in homozygous mutants

increased T cell number ( J:106040 )

• peripheral blood T-lymphocyte numbers are greatly elevated in 40% of mice with thymic lymphoma

increased IgM level ( J:106040 )

• circulating IgM levels in mutant mice are elevated to 3-fold wild-type levels

hematopoietic system

small thymus ( J:106040 )

increased T cell derived lymphoma incidence ( J:106040 )

• in 40% of mice with thymic lymphoma, lymphoma cells are present in the periphery where they greatly elevate peripheral blood lymphocyte numbers, form spleen and/or lymph node tumors, and invade nonhematopoietic organs

• T-cell lymphoma cells of homozygous mutant mice vary in their expression of CD4 and CD8 and are CD3^dim

• lymphoma cells of mutant mice express terminal deoxynucleotide transferase, a characteristic of immature T lymphoblast cells

• the lymphoma cells, unlike ordinary T-cell progenitor cells in these mice, express only low levels of PU.1/SFPI1

• analysis of the TCR-beta variable-region isotype of T-cell lymphoma cells from lymph node tumors indicates they are clonally derived

• a characteristic pattern of promoter hypermethylation is detected by RLGS analysis in T-cell lymphomas (but not in myeloid tumors) of homozygous mutant mice

• hypermethylation and transcriptional downregulation of the inhibitor of DNA binding 4 (Id4) tumor suppressor gene is characteristic of T-cell lymphomas, but not of myeloid tumors, of homozygous mutant mice

• T-cell lymphomas of these mice exhibit a characteristic pattern of promoter hypermethylation that is not shared by myeloid tumors in the same mice; inhibitor of DNA binding 4 (Id4, aka Idb4) is reproducibly hypermethylated and downregulated in these but not AML

• injection of lymphoma cells transmits the phenoytpe to NOD.CB17-Prkdc^scid mice, causing death within 3-6 weeks

decreased pro-B cell number ( J:106040 )

• numbers of bone marrow pro-B cells (Lin^-IgM^-B220⁺CD43⁺) are greatly reduced

arrested B cell differentiation ( J:106040 )

• B cell differentiation is blocked before the pro-B cell stage in mutant mice, as numbers of bone marrow pro-B cells (Lin^-IgM^-B220⁺CD43⁺) and pre-B cells (Lin^-IgM^-B220⁺CD43^-) are greatly reduced

abnormal double-negative T cell morphology ( J:106040 )

• SFPI1/PU.1 is expressed at higher levels in mutant than in wild-type ETPs and DN1-DN3 thymocytes, but is turned off in both mutant and wild-type CD4⁺CD8⁺ (double positive, DP) thymocytes

decreased granulocyte number ( J:106040 )

• proportion of myeloid cells (Mac1^lowIgm^-) in the peritoneum diminishes over time

decreased mature B cell number ( J:106040 )

• mature B cell numbers are greatly reduced in bone marrow, spleen and liver of homozygous mutant mice

decreased B-1a cell number ( J:106040 )

• the intraperitoneal B1 cell population is skewed toward B1b cells (CD5^-), with concomitant reduction of the proportion of B1a cells (CD5⁺) from the 30-40% seen in wild-type mice to ~10-20% in homozygous mutants

decreased pre-B cell number ( J:106040 )

• numbers of bone marrow pre-B cells (Lin^-IgM^-B220⁺CD43^-) are greatly reduced

abnormal T cell subpopulation ratio ( J:106040 )

• the proportion of immature, CD4^-CD8^- (double negative, DN) thymocytes is elevated

• within the DN thymocyte population, the proportions of early, DN1-DN2 stage thymocytes are elevated, while later, DN3-DN4 stage thymocyte percentages are reduced

• mutant thymi contain elevated numbers of the earliest T cell lineage-restricted progenitor cells (ETPs, CD3^-CD4^-CD8^-Kit^bright), but reduced numbers of proT and preT cells

decreased T cell number ( J:106040 )

• numbers of mature CD4⁺ and CD8⁺ T cells in the periphery are slightly reduced in mutant mice

decreased thymocyte number ( J:106040 )

• thymi of mutant mice contain 3.4-fold fewer thymocytes than those of wild-type mice

increased lymphocyte cell number ( J:106040 )

• intraperitoneal lymphocyte numbers in mutant mice increase progressively with age, to greater than 3-fold wild-type numbers by 4-8 months

increased B-1 B cell number ( J:106040 )

• the percentage of physically and functionally normal B1 cells (Mac1^lowIgM^highCD43⁺B7.1⁺CD23^-CD19⁺B220^low) in the peritoneum increases with time

• B1 cells account for up to 43% of peripheral blood lymphocytes in older mutant mice, although they are not present in blood of wild-type mice

• Southern blot analysis of peritoneal lymphocytes for IghD-J rearrangements found evidence of clonal B1 cell proliferation in one mutant mouse of 6 studied at ages 6-8 mo

increased B-1b cell number ( J:106040 )

• the intraperitoneal B1 cell population is skewed toward B1b cells (CD5^-), with concomitant reduction of the proportion of B1a cells (CD5⁺) from the 30-40% seen in wild-type mice to ~10-20% in homozygous mutants

increased T cell number ( J:106040 )

• peripheral blood T-lymphocyte numbers are greatly elevated in 40% of mice with thymic lymphoma

increased IgM level ( J:106040 )

• circulating IgM levels in mutant mice are elevated to 3-fold wild-type levels

endocrine/exocrine glands

small thymus ( J:106040 )

decreased thymocyte number ( J:106040 )

• thymi of mutant mice contain 3.4-fold fewer thymocytes than those of wild-type mice

increased T cell derived lymphoma incidence ( J:106040 )

• in 40% of mice with thymic lymphoma, lymphoma cells are present in the periphery where they greatly elevate peripheral blood lymphocyte numbers, form spleen and/or lymph node tumors, and invade nonhematopoietic organs

• T-cell lymphoma cells of homozygous mutant mice vary in their expression of CD4 and CD8 and are CD3^dim

• lymphoma cells of mutant mice express terminal deoxynucleotide transferase, a characteristic of immature T lymphoblast cells

• the lymphoma cells, unlike ordinary T-cell progenitor cells in these mice, express only low levels of PU.1/SFPI1

• analysis of the TCR-beta variable-region isotype of T-cell lymphoma cells from lymph node tumors indicates they are clonally derived

• a characteristic pattern of promoter hypermethylation is detected by RLGS analysis in T-cell lymphomas (but not in myeloid tumors) of homozygous mutant mice

• hypermethylation and transcriptional downregulation of the inhibitor of DNA binding 4 (Id4) tumor suppressor gene is characteristic of T-cell lymphomas, but not of myeloid tumors, of homozygous mutant mice

• T-cell lymphomas of these mice exhibit a characteristic pattern of promoter hypermethylation that is not shared by myeloid tumors in the same mice; inhibitor of DNA binding 4 (Id4, aka Idb4) is reproducibly hypermethylated and downregulated in these but not AML

• injection of lymphoma cells transmits the phenoytpe to NOD.CB17-Prkdc^scid mice, causing death within 3-6 weeks