Phenotypes associated with this allele

• Allele Symbol: Ikzf1⁺
• Allele Name: wild type
• Allele ID: MGI:2436731
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Ikzf1^plstc/Ikzf1^+	C57BL/6JSfdAnu-Ikzf1^plstc	MGI:2670891
ht2	Ikzf1^tm1.1(Pax5)Mbu/Ikzf1^+	involves: 129P2/OlaHsd * C57BL/6	MGI:2653528
ht3	Ikzf1^tm1Kge/Ikzf1^+	involves: 129S4/SvJae * BALB/c	MGI:4360784
ht4	Ikzf1^tm1Kge/Ikzf1^+	involves: 129S4/SvJae * C57BL/6	MGI:4360783
cn5	Ikzf1^tm1.1(Pax5)Mbu/Ikzf1^+ Tcf3^tm1Mbu/Tcf3^tm1Mbu Commd10^Tg(Vav1-icre)A2Kio/Commd10^+	involves: 129P2/OlaHsd * C57BL/10 * CBA/Ca	MGI:3804204
cn6	Ikzf1^tm1(Pax5)Mbu/Ikzf1^+ Tg(Lck-cre)1Cwi/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3701081
cx7	Ikzf1^tm1Kast/Ikzf1^+ Tg(BCR/ABL)623Hkp/0	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:4819230

Genotype
MGI:2670891

ht1

• Allelic Composition: Ikzf1^plstc/Ikzf1⁺
• Genetic Background: C57BL/6JSfdAnu-Ikzf1^plstc

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

mortality/aging

premature death ( J:84569 )

• heterozygotes show a decline in survival after 2 months of age, with 65% dying at ~4 months of age with T cell leukemia/lymphomas

neoplasm

increased T cell derived lymphoma incidence ( J:84569 )

• >65% of heterozygotes develop T cell lymphomas at an average age of 120 days

• the predominant malignant cell type is positive for the CD3-TCRalphabeta complex and Thy1

• individual lymphomas vary in stage of T cell maturity, with CD44^-25^-4^-8⁺ and CD44^-25^-4⁺8⁺ stages of differentiation found in 32.5% of heterozygotes

increased leukemia incidence ( J:84569 )

hematopoietic system

decreased thymocyte number ( J:84569 )

• at E15.5, thymocyte numbers are reduced to 50% of wild-type controls

abnormal lymphopoiesis ( J:84569 )

• heterozygotes display a partial block in lymphopoiesis

abnormal B cell differentiation ( J:84569 )

• at E15.5, B cell differentiation fails to progress beyond the B220⁺CD19^- stage in fetal liver, unlike in wild-type controls; however, normal numbers of B220⁺CD19⁺ cells are found in bone marrow at 4 weeks after birth

• at 4 weeks of age, B cell differentiation past the IgH-gene rearrangement checkpoint is reduced in the bone marrow; however, B cells that overcome this partial block establish normal mature B cell compartments and express normal levels of IgM, IgD, CD21 and CD23

increased pro-B cell number ( J:84569 )

• at 4 weeks of age, heterozygotes show significant accumulation of B220^loCD43⁺ pro-B cells (180%) in the bone marrow

abnormal T cell differentiation ( J:84569 )

• at E15.5, heterozygotes display an incomplete block in T cell differentiation relative to wild-type controls

• however, normal subsets of thymocytes and mature T cells are found at 4 weeks after birth, with significantly higher numbers of total Thy1⁺ cells in spleen (145%), consistent with a preleukemic stage

decreased double-negative T cell number ( J:84569 )

• at E15.5, double-negative Thy1⁺ precursor numbers are reduced to 50% of wild-type controls

decreased double-positive T cell number ( J:84569 )

• at E15.5, heterozygotes lack double-positive Thy1⁺ precursor cells

myeloid hyperplasia ( J:84569 )

• at E15.5, heterozygotes show an intermediate level of myeloid hyperplasia in fetal liver

• however, Gr-1^hi cell numbers are normal, indicating that terminal granulocyte differentiation is not impaired in fetal liver

decreased mature B cell number ( J:84569 )

• at 4 weeks of age, heterozygotes show a 50% reduction in B220^hiCD43^- mature B cells in the bone marrow

decreased pre-B cell number ( J:84569 )

• at 4 weeks of age, heterozygotes show a 20% reduction in B220^loCD43^- pre-B cells in the bone marrow

immune system

decreased thymocyte number ( J:84569 )

• at E15.5, thymocyte numbers are reduced to 50% of wild-type controls

abnormal lymphopoiesis ( J:84569 )

• heterozygotes display a partial block in lymphopoiesis

abnormal B cell differentiation ( J:84569 )

• at E15.5, B cell differentiation fails to progress beyond the B220⁺CD19^- stage in fetal liver, unlike in wild-type controls; however, normal numbers of B220⁺CD19⁺ cells are found in bone marrow at 4 weeks after birth

• at 4 weeks of age, B cell differentiation past the IgH-gene rearrangement checkpoint is reduced in the bone marrow; however, B cells that overcome this partial block establish normal mature B cell compartments and express normal levels of IgM, IgD, CD21 and CD23

increased pro-B cell number ( J:84569 )

• at 4 weeks of age, heterozygotes show significant accumulation of B220^loCD43⁺ pro-B cells (180%) in the bone marrow

abnormal T cell differentiation ( J:84569 )

• at E15.5, heterozygotes display an incomplete block in T cell differentiation relative to wild-type controls

• however, normal subsets of thymocytes and mature T cells are found at 4 weeks after birth, with significantly higher numbers of total Thy1⁺ cells in spleen (145%), consistent with a preleukemic stage

decreased double-negative T cell number ( J:84569 )

• at E15.5, double-negative Thy1⁺ precursor numbers are reduced to 50% of wild-type controls

decreased double-positive T cell number ( J:84569 )

• at E15.5, heterozygotes lack double-positive Thy1⁺ precursor cells

myeloid hyperplasia ( J:84569 )

• at E15.5, heterozygotes show an intermediate level of myeloid hyperplasia in fetal liver

• however, Gr-1^hi cell numbers are normal, indicating that terminal granulocyte differentiation is not impaired in fetal liver

decreased mature B cell number ( J:84569 )

• at 4 weeks of age, heterozygotes show a 50% reduction in B220^hiCD43^- mature B cells in the bone marrow

decreased pre-B cell number ( J:84569 )

• at 4 weeks of age, heterozygotes show a 20% reduction in B220^loCD43^- pre-B cells in the bone marrow

liver/biliary system

liver hypoplasia ( J:84569 )

• at E15.5, fetal liver cellularity is moderately decreased relative to that in wild-type controls

endocrine/exocrine glands

decreased thymocyte number ( J:84569 )

• at E15.5, thymocyte numbers are reduced to 50% of wild-type controls

increased T cell derived lymphoma incidence ( J:84569 )

• >65% of heterozygotes develop T cell lymphomas at an average age of 120 days

• the predominant malignant cell type is positive for the CD3-TCRalphabeta complex and Thy1

• individual lymphomas vary in stage of T cell maturity, with CD44^-25^-4^-8⁺ and CD44^-25^-4⁺8⁺ stages of differentiation found in 32.5% of heterozygotes

Genotype
MGI:2653528

ht2

• Allelic Composition: Ikzf1^{tm1.1(Pax5)Mbu}/Ikzf1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:118111 )

• mice die between 2 and 4 months of age

hematopoietic system

enlarged thymus ( J:118111 )

thymus hypoplasia ( J:118111 )

• significantly reduced at 2 weeks relative to Igh^tm1(PAX5)Mbu homozygotes

enlarged spleen ( J:118111 )

abnormal erythropoiesis ( J:80815 )

• number of erythroid precursors in bone marrow decreases to 1/20 of control numbers by 8 weeks of age

abnormal B cell differentiation ( J:80815 )

increased pro-B cell number ( J:80815 )

• at 8 weeks, number of pro-B cells is still 3.5-fold greater than controls

decreased double-positive T cell number ( J:118111 )

• significantly reduced at 2 weeks relative to Igh^tm1(PAX5)Mbu homozygotes

increased B cell number ( J:80815 )

• at E18.5, there are ~7-fold more B lymphocytes than in controls

immune system

enlarged thymus ( J:118111 )

thymus hypoplasia ( J:118111 )

• significantly reduced at 2 weeks relative to Igh^tm1(PAX5)Mbu homozygotes

enlarged spleen ( J:118111 )

abnormal B cell differentiation ( J:80815 )

increased pro-B cell number ( J:80815 )

• at 8 weeks, number of pro-B cells is still 3.5-fold greater than controls

decreased double-positive T cell number ( J:118111 )

• significantly reduced at 2 weeks relative to Igh^tm1(PAX5)Mbu homozygotes

increased B cell number ( J:80815 )

• at E18.5, there are ~7-fold more B lymphocytes than in controls

enlarged lymph nodes ( J:118111 )

neoplasm

increased lymphoma incidence ( J:118111 )

• lymphoid organs show diffuse infiltration by diffuse lymphoblastic lymphoma

• extensive tumor infiltrates are found in other organs including heart, kidneys, lungs, liver, intestine and testis

increased T cell derived lymphoma incidence ( J:118111 )

endocrine/exocrine glands

enlarged thymus ( J:118111 )

thymus hypoplasia ( J:118111 )

• significantly reduced at 2 weeks relative to Igh^tm1(PAX5)Mbu homozygotes

increased T cell derived lymphoma incidence ( J:118111 )

growth/size/body

enlarged spleen ( J:118111 )

Genotype
MGI:4360784

ht3

• Allelic Composition: Ikzf1^tm1Kge/Ikzf1⁺
• Genetic Background: involves: 129S4/SvJae * BALB/c

mortality/aging

premature death ( J:29355 )

• mice develop a fatal leukemia between 3 and 6 months of age

neoplasm

increased leukemia incidence ( J:29355 )

• leukemia derived from alpha-beta T cells occurs in all mice

• the cells are large, can be either CD4⁺ or CD8⁺, and are monoclonal in their use of TCR beta chains

• these lymphoblastic cells accumulate in all immune organs and in the liver, kidney, and lung

• leukemia cells disrupt the architecture of numerous organs as the mice age

• studies with 2-month old mice suggest the malignant cells arise in the thymus and not in the spleen

immune system

increased T cell proliferation ( J:29355 )

• basal proliferation of T cells is 2.6 fold higher than controls

abnormal thymus lobule morphology ( J:29355 )

• leukemia leads to the loss of the bi-lobed structure of the thymus in mice over 3 months of age

thymus cortex hypoplasia ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

abnormal thymus medulla morphology ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

enlarged thymus ( J:29355 )

• leukemia leads to a swelling of the thymus in mice over 3 months of age

abnormal thymocyte activation ( J:29355 )

• thymocytes from 1 month old mice have a 200-fold increase in their proliferation rate in response to TCR stimulus compared to controls

• a less dramatic increase in proliferation rate is observed with thymocytes from E18.5 fetuses

spleen hyperplasia ( J:29355 )

• splenocyte numbers are 2- to 5- fold greater than controls by 3 months of age

• leukemia later in life leads to spleen cellularity that is 10-fold greater than normal

abnormal T cell differentiation ( J:29355 )

• starting at ages 2-3 months, intermediate single positive thymoyctes start accumulating

decreased spleen red pulp amount ( J:29355 )

• leukemia leads to an decrease in the red pulp area of the spleen

increased spleen white pulp amount ( J:29355 )

• leukemia leads to an increase in the white pulp area of the spleen

enlarged mesenteric lymph nodes ( J:29355 )

• leukemia results in enlarged lymph nodes for all mice over 3 months of age

• lymph nodes enlarge 20- to 50- fold greater than normal

abnormal lymph node cortex morphology ( J:29355 )

• leukemia leads to the loss of lymph node structure

abnormal lymph node medulla morphology ( J:29355 )

• leukemia leads to the loss of lymph node structure

lymph node hyperplasia ( J:29355 )

• leukemia results in enlarged lymph nodes for all mice over 3 months of age

• lymph nodes enlarge 20- to 50- fold greater than normal

enlarged cervical lymph nodes ( J:29355 )

• leukemia results in enlarged lymph nodes for all mice over 3 months of age

• lymph nodes enlarge 20- to 50- fold greater than normal

hematopoietic system

increased T cell proliferation ( J:29355 )

• basal proliferation of T cells is 2.6 fold higher than controls

abnormal thymus lobule morphology ( J:29355 )

• leukemia leads to the loss of the bi-lobed structure of the thymus in mice over 3 months of age

thymus cortex hypoplasia ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

abnormal thymus medulla morphology ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

enlarged thymus ( J:29355 )

• leukemia leads to a swelling of the thymus in mice over 3 months of age

abnormal thymocyte activation ( J:29355 )

• thymocytes from 1 month old mice have a 200-fold increase in their proliferation rate in response to TCR stimulus compared to controls

• a less dramatic increase in proliferation rate is observed with thymocytes from E18.5 fetuses

spleen hyperplasia ( J:29355 )

• splenocyte numbers are 2- to 5- fold greater than controls by 3 months of age

• leukemia later in life leads to spleen cellularity that is 10-fold greater than normal

abnormal T cell differentiation ( J:29355 )

• starting at ages 2-3 months, intermediate single positive thymoyctes start accumulating

decreased spleen red pulp amount ( J:29355 )

• leukemia leads to an decrease in the red pulp area of the spleen

increased spleen white pulp amount ( J:29355 )

• leukemia leads to an increase in the white pulp area of the spleen

endocrine/exocrine glands

abnormal thymus lobule morphology ( J:29355 )

• leukemia leads to the loss of the bi-lobed structure of the thymus in mice over 3 months of age

thymus cortex hypoplasia ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

abnormal thymus medulla morphology ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

enlarged thymus ( J:29355 )

• leukemia leads to a swelling of the thymus in mice over 3 months of age

abnormal thymocyte activation ( J:29355 )

• thymocytes from 1 month old mice have a 200-fold increase in their proliferation rate in response to TCR stimulus compared to controls

• a less dramatic increase in proliferation rate is observed with thymocytes from E18.5 fetuses

cellular

increased T cell proliferation ( J:29355 )

• basal proliferation of T cells is 2.6 fold higher than controls

growth/size/body

spleen hyperplasia ( J:29355 )

• splenocyte numbers are 2- to 5- fold greater than controls by 3 months of age

• leukemia later in life leads to spleen cellularity that is 10-fold greater than normal

Genotype
MGI:4360783

ht4

• Allelic Composition: Ikzf1^tm1Kge/Ikzf1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:29355 )

• mice develop a fatal leukemia between 3 and 6 months of age

neoplasm

increased leukemia incidence ( J:29355 )

• leukemia derived from alpha-beta T cells occurs in all mice

• the cells are large, can be either CD4⁺ or CD8⁺, and are monoclonal in their use of TCR beta chains

• these lymphoblastic cells accumulate in all immune organs and in the liver, kidney, and lung

• leukemia cells disrupt the architecture of numerous organs as the mice age

• studies with 2-month old mice suggest the malignant cells arise in the thymus and not in the spleen

immune system

increased T cell proliferation ( J:29355 )

• basal proliferation of T cells is 2.6 fold higher than controls

abnormal thymus lobule morphology ( J:29355 )

• leukemia leads to the loss of the bi-lobed structure of the thymus in mice over 3 months of age

thymus cortex hypoplasia ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

abnormal thymus medulla morphology ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

enlarged thymus ( J:29355 )

• leukemia leads to a swelling of the thymus in mice over 3 months of age

abnormal thymocyte activation ( J:29355 )

• thymocytes from 1 month old mice have a 200-fold increase in their proliferation rate in response to TCR stimulus compared to controls

• a less dramatic increase in proliferation rate is observed with thymocytes from E18.5 fetuses

spleen hyperplasia ( J:29355 )

• splenocyte numbers are 2- to 5- fold greater than controls by 3 months of age

• leukemia later in life leads to spleen cellularity that is 10-fold greater than normal

abnormal T cell differentiation ( J:29355 )

• starting at ages 2-3 months, intermediate single positive thymoyctes start accumulating

decreased spleen red pulp amount ( J:29355 )

• leukemia leads to an decrease in the red pulp area of the spleen

increased spleen white pulp amount ( J:29355 )

• leukemia leads to an increase in the white pulp area of the spleen

enlarged mesenteric lymph nodes ( J:29355 )

• leukemia results in enlarged lymph nodes for all mice over 3 months of age

• lymph nodes enlarge 20- to 50- fold greater than normal

abnormal lymph node cortex morphology ( J:29355 )

• leukemia leads to the loss of lymph node structure

abnormal lymph node medulla morphology ( J:29355 )

• leukemia leads to the loss of lymph node structure

lymph node hyperplasia ( J:29355 )

• leukemia results in enlarged lymph nodes for all mice over 3 months of age

• lymph nodes enlarge 20- to 50- fold greater than normal

enlarged cervical lymph nodes ( J:29355 )

• leukemia results in enlarged lymph nodes for all mice over 3 months of age

• lymph nodes enlarge 20- to 50- fold greater than normal

hematopoietic system

increased T cell proliferation ( J:29355 )

• basal proliferation of T cells is 2.6 fold higher than controls

abnormal thymus lobule morphology ( J:29355 )

• leukemia leads to the loss of the bi-lobed structure of the thymus in mice over 3 months of age

thymus cortex hypoplasia ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

abnormal thymus medulla morphology ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

enlarged thymus ( J:29355 )

• leukemia leads to a swelling of the thymus in mice over 3 months of age

abnormal thymocyte activation ( J:29355 )

• thymocytes from 1 month old mice have a 200-fold increase in their proliferation rate in response to TCR stimulus compared to controls

• a less dramatic increase in proliferation rate is observed with thymocytes from E18.5 fetuses

spleen hyperplasia ( J:29355 )

• splenocyte numbers are 2- to 5- fold greater than controls by 3 months of age

• leukemia later in life leads to spleen cellularity that is 10-fold greater than normal

abnormal T cell differentiation ( J:29355 )

• starting at ages 2-3 months, intermediate single positive thymoyctes start accumulating

decreased spleen red pulp amount ( J:29355 )

• leukemia leads to an decrease in the red pulp area of the spleen

increased spleen white pulp amount ( J:29355 )

• leukemia leads to an increase in the white pulp area of the spleen

endocrine/exocrine glands

abnormal thymus lobule morphology ( J:29355 )

• leukemia leads to the loss of the bi-lobed structure of the thymus in mice over 3 months of age

thymus cortex hypoplasia ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

abnormal thymus medulla morphology ( J:29355 )

• leukemia in older mice leads to complete effacement of cortical and medullary structures in the thymus

enlarged thymus ( J:29355 )

• leukemia leads to a swelling of the thymus in mice over 3 months of age

abnormal thymocyte activation ( J:29355 )

• thymocytes from 1 month old mice have a 200-fold increase in their proliferation rate in response to TCR stimulus compared to controls

• a less dramatic increase in proliferation rate is observed with thymocytes from E18.5 fetuses

cellular

increased T cell proliferation ( J:29355 )

• basal proliferation of T cells is 2.6 fold higher than controls

growth/size/body

spleen hyperplasia ( J:29355 )

• splenocyte numbers are 2- to 5- fold greater than controls by 3 months of age

• leukemia later in life leads to spleen cellularity that is 10-fold greater than normal

Genotype
MGI:3804204

cn5

• Allelic Composition: Ikzf1^{tm1.1(Pax5)Mbu}/Ikzf1⁺; Tcf3^tm1Mbu/Tcf3^tm1Mbu; Commd10^{Tg(Vav1-icre)A2Kio}/Commd10⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/10 * CBA/Ca

immune system

immune system phenotype ( J:137719 )

N • development of pro-B cells is rescued

abnormal immunoglobulin heavy chain V(D)J recombination ( J:137719 )

• proximal VH7183-DJH and distal VHJ558-DJH rearrangements of the IgH are reduced compared to in wild-type mice

• Vk-Jk recombination of the Igk locus is absent

hematopoietic system

abnormal immunoglobulin heavy chain V(D)J recombination ( J:137719 )

• proximal VH7183-DJH and distal VHJ558-DJH rearrangements of the IgH are reduced compared to in wild-type mice

• Vk-Jk recombination of the Igk locus is absent

Genotype
MGI:3701081

cn6

• Allelic Composition: Ikzf1^tm1(Pax5)Mbu/Ikzf1⁺; Tg(Lck-cre)1Cwi/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

neoplasm

increased T cell derived lymphoma incidence ( J:118111 )

• immature T cell lymphomas develop with shorter latency than in Igh^tm1(PAX5)Mbu homozygotes

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:118111 )

• immature T cell lymphomas develop with shorter latency than in Igh^tm1(PAX5)Mbu homozygotes

Genotype
MGI:4819230

cx7

• Allelic Composition: Ikzf1^tm1Kast/Ikzf1⁺; Tg(BCR/ABL)623Hkp/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA

neoplasm

increased acute lymphoblastic leukemia incidence ( J:160846 )

• mice develop B cell acute lymphoblastic leukemia with a median latency of 5.7 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute lymphoblastic leukemia		DOID:9952	OMIM:247640 OMIM:613065	J:160846