Phenotypes associated with this allele

• Allele Symbol: Rag1^tm1Jsek
• Allele Name: targeted mutation 1, JoAnne Sekiguchi
• Allele ID: MGI:3840831
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rag1^tm1Jsek/Rag1^tm1Jsek	involves: 129S6/SvEvTac	MGI:3840832
ht2	Rag1^tm1Jsek/Rag1^+	involves: 129S6/SvEvTac	MGI:3840833
cx3	Rag1^tm1Jsek/Rag1^tm1Jsek Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * 129S6/SvEvTac	MGI:3840834

Genotype
MGI:3840832

hm1

• Allelic Composition: Rag1^tm1Jsek/Rag1^tm1Jsek
• Genetic Background: involves: 129S6/SvEvTac

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

immune system

thymus hypoplasia ( J:146912 )

• thymus cellularity is reduced 20- to a 100-fold in mice 5 to 6 weeks of age

abnormal lymphopoiesis ( J:146912 )

absent immature B cells ( J:146912 )

• immature B220⁺IgM⁺ B cells are absent from the bone marrow

abnormal immunoglobulin heavy chain V(D)J recombination ( J:146912 )

• IgH-D to IgH-J rearrangements are severely impaired in sorted pro-B- and pre-B-cell populations

increased pro-B cell number ( J:146912 )

• pro-B cell numbers are increased in the bone marrow due to block in B cell development

arrested B cell differentiation ( J:146912 )

• B cell development is completely arrested at the B220⁺CD43⁺ stage

abnormal T cell receptor V(D)J recombination ( J:146912 )

• interchromosomal trans-rearrangement between Tcrg-variable segments and Tcrb-joining segments are detected in thymocytes

abnormal T cell receptor beta chain V(D)J recombination ( J:146912 )

• Dbeta to Jbeta rearrangements are severely impaired in thymocytes

increased double-negative T cell number ( J:146912 )

• there is an increased percentage of thymocytes at the DN3 (CD44^-CD25⁺) stage

decreased double-positive T cell number ( J:146912 )

• a very small number of double-positive T cells are observed in the thymus of most mice

• a minority of mice have no detectable double-positive T cells

arrested T cell differentiation ( J:146912 )

• vast majority of thymocytes arrest development at the DN3 (CD44^-CD25⁺) stage

absent mature B cells ( J:146912 )

• mature B220⁺IgM⁺ B cells are absent from the periphery

decreased CD4-positive, alpha-beta T cell number ( J:146912 )

• a very small number of CD4⁺ T cells are found in the thymus and lymph nodes

decreased CD8-positive, alpha-beta T cell number ( J:146912 )

• a very small number of CD8⁺ T cells are found in the thymus and lymph nodes

decreased gamma-delta T cell number ( J:146912 )

• gammadelta T cell numbers are dramatically reduced both in the thymus and in the periphery

abnormal immunoglobulin level ( J:146912 )

• majority of mice have substantially lower levels of IgE

• however, almost a third have mice have IgE levels that are 5- to 10- fold higher than wild-type controls

cellular

spontaneous chromosome breakage ( J:146912 )

• interchromosomal trans-rearrangement between Tcrg-variable segments and Tcrb-joining segments are detected in thymocytes

hematopoietic system

thymus hypoplasia ( J:146912 )

• thymus cellularity is reduced 20- to a 100-fold in mice 5 to 6 weeks of age

abnormal lymphopoiesis ( J:146912 )

absent immature B cells ( J:146912 )

• immature B220⁺IgM⁺ B cells are absent from the bone marrow

abnormal immunoglobulin heavy chain V(D)J recombination ( J:146912 )

• IgH-D to IgH-J rearrangements are severely impaired in sorted pro-B- and pre-B-cell populations

increased pro-B cell number ( J:146912 )

• pro-B cell numbers are increased in the bone marrow due to block in B cell development

arrested B cell differentiation ( J:146912 )

• B cell development is completely arrested at the B220⁺CD43⁺ stage

abnormal T cell receptor V(D)J recombination ( J:146912 )

• interchromosomal trans-rearrangement between Tcrg-variable segments and Tcrb-joining segments are detected in thymocytes

abnormal T cell receptor beta chain V(D)J recombination ( J:146912 )

• Dbeta to Jbeta rearrangements are severely impaired in thymocytes

increased double-negative T cell number ( J:146912 )

• there is an increased percentage of thymocytes at the DN3 (CD44^-CD25⁺) stage

decreased double-positive T cell number ( J:146912 )

• a very small number of double-positive T cells are observed in the thymus of most mice

• a minority of mice have no detectable double-positive T cells

arrested T cell differentiation ( J:146912 )

• vast majority of thymocytes arrest development at the DN3 (CD44^-CD25⁺) stage

absent mature B cells ( J:146912 )

• mature B220⁺IgM⁺ B cells are absent from the periphery

decreased CD4-positive, alpha-beta T cell number ( J:146912 )

• a very small number of CD4⁺ T cells are found in the thymus and lymph nodes

decreased CD8-positive, alpha-beta T cell number ( J:146912 )

• a very small number of CD8⁺ T cells are found in the thymus and lymph nodes

decreased gamma-delta T cell number ( J:146912 )

• gammadelta T cell numbers are dramatically reduced both in the thymus and in the periphery

abnormal immunoglobulin level ( J:146912 )

• majority of mice have substantially lower levels of IgE

• however, almost a third have mice have IgE levels that are 5- to 10- fold higher than wild-type controls

endocrine/exocrine glands

thymus hypoplasia ( J:146912 )

• thymus cellularity is reduced 20- to a 100-fold in mice 5 to 6 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Omenn syndrome	DOID:0060010	OMIM:603554	J:146912

Genotype
MGI:3840833

ht2

• Allelic Composition: Rag1^tm1Jsek/Rag1⁺
• Genetic Background: involves: 129S6/SvEvTac

immune system

abnormal B cell differentiation ( J:146912 )

• B cell development becomes impaired in mice over 1 year of age

• in the bone marrow of year old mice, significantly fewer B220⁺CD43⁺ pro-B cells progress to the B220⁺CD43^- pre-B and B220⁺IgM⁺ stages of development

abnormal immunoglobulin heavy chain V(D)J recombination ( J:146912 )

• IgH-D to IgH-J rearrangements are impaired in sorted pro-B- and pre-B-cell populations of mice one year of age compared to controls

abnormal T cell differentiation ( J:146912 )

• T cell development becomes impaired in mice over 1 year of age

• there is a significant decrease in the percentage and number of double-positive thymocytes of year old mice compared to age-matched wild-type controls

abnormal T cell receptor beta chain V(D)J recombination ( J:146912 )

• Dbeta to Jbeta rearrangements are impaired in thymocytes of mice over 1 year of age compared to controls

decreased double-positive T cell number ( J:146912 )

• there is a significant decrease in the percentage and number of double-positive thymocytes of year old mice compared to age-matched wild-type controls

hematopoietic system

abnormal B cell differentiation ( J:146912 )

• B cell development becomes impaired in mice over 1 year of age

• in the bone marrow of year old mice, significantly fewer B220⁺CD43⁺ pro-B cells progress to the B220⁺CD43^- pre-B and B220⁺IgM⁺ stages of development

abnormal immunoglobulin heavy chain V(D)J recombination ( J:146912 )

• IgH-D to IgH-J rearrangements are impaired in sorted pro-B- and pre-B-cell populations of mice one year of age compared to controls

abnormal T cell differentiation ( J:146912 )

• T cell development becomes impaired in mice over 1 year of age

• there is a significant decrease in the percentage and number of double-positive thymocytes of year old mice compared to age-matched wild-type controls

abnormal T cell receptor beta chain V(D)J recombination ( J:146912 )

• Dbeta to Jbeta rearrangements are impaired in thymocytes of mice over 1 year of age compared to controls

decreased double-positive T cell number ( J:146912 )

• there is a significant decrease in the percentage and number of double-positive thymocytes of year old mice compared to age-matched wild-type controls

Genotype
MGI:3840834

cx3

• Allelic Composition: Rag1^tm1Jsek/Rag1^tm1Jsek; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac

mortality/aging

decreased survivor rate ( J:146912 )

• mice have significantly decreased survival compared to Trp53^tm1Tyj homozygote controls

premature death ( J:146912 )

• all mice die from lymphomas by 30 weeks of age

neoplasm

increased T cell derived lymphoma incidence ( J:146912 )

• 90% of lymphomas in these mice are immature TCRbeta^- T cell lymphomas

• thymic lymphomas feature frequent clonal translocations and fusions that are karyotypically distinct from lymphomas isolated from Trp53^tm1Tyj homozygotes

cellular

spontaneous chromosome breakage ( J:146912 )

• 6 of 7 lymphomas contain chromosomal translocations and/or short-arm fusions in a clonal population of tumor cells

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:146912 )

• 90% of lymphomas in these mice are immature TCRbeta^- T cell lymphomas

• thymic lymphomas feature frequent clonal translocations and fusions that are karyotypically distinct from lymphomas isolated from Trp53^tm1Tyj homozygotes

immune system

increased T cell derived lymphoma incidence ( J:146912 )

• 90% of lymphomas in these mice are immature TCRbeta^- T cell lymphomas

• thymic lymphomas feature frequent clonal translocations and fusions that are karyotypically distinct from lymphomas isolated from Trp53^tm1Tyj homozygotes

hematopoietic system

increased T cell derived lymphoma incidence ( J:146912 )

• 90% of lymphomas in these mice are immature TCRbeta^- T cell lymphomas

• thymic lymphomas feature frequent clonal translocations and fusions that are karyotypically distinct from lymphomas isolated from Trp53^tm1Tyj homozygotes