All Phenotypes Igh-J<tm2(3H9-VDJ*)Mwg> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Igh-J^{tm2(3H9-VDJ*)Mwg}
targeted mutation 2, Martin Weigert
MGI:3762369

Summary

6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺	B6.129P2-Igh-J^{tm2(3H9-VDJ*)Mwg}	MGI:3836920
ht2	Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺	involves: 129P2/OlaHsd * BALB/c	MGI:3809237
ht3	Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺	involves: 129P2/OlaHsd * BALB/c * C57BL/6	MGI:3809011
cx4	Tcrb^tm1Mom/Tcrb^tm1Mom Tcrd^tm1Mom/Tcrd^tm1Mom Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺	B6.129P2-Tcrb^tm1Mom Igh-J^{tm2(3H9-VDJ*)Mwg} Tcrd^tm1Mom	MGI:3836921
cx5	Cd4^tm1Mak/Cd4^tm1Mak Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺	B6.Cg-Cd4^tm1Mak Igh-J^{tm2(3H9-VDJ*)Mwg}	MGI:3836922
cx6	Fas^lpr/Fas^lpr Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺	MRL.Cg-Fas^lpr Igh-J^{tm2(3H9-VDJ*)Mwg}	MGI:3809239

Allelic Composition	Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺
Genetic Background	B6.129P2-Igh-J^{tm2(3H9-VDJ*)Mwg}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igh-J^{tm2(3H9-VDJ*)Mwg} mutation (3 available); any Igh-J mutation (13 available)

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

immune system

increased marginal zone B cell number ( J:142389 )

• relative numbers of marginal B cells is increased more than 3-fold compared to wild-type controls

decreased B cell number ( J:142389 )

• mice have 2.4-fold fewer B cells than controls

spleen hypoplasia ( J:142389 )

• spleen has 1.6-fold fewer B cells than controls

increased anti-double stranded DNA antibody level ( J:142389 )

• anti-dsDNA antibodies of the IgG2a isotype are detected in the sera of mice with levels dropping between 6 and 12 months of age

• anti-dsDNA antibodies with IgM, IgG2b, IgG3 isotypes are also present in mice at 6 months of age

hematopoietic system

increased marginal zone B cell number ( J:142389 )

• relative numbers of marginal B cells is increased more than 3-fold compared to wild-type controls

decreased B cell number ( J:142389 )

• mice have 2.4-fold fewer B cells than controls

spleen hypoplasia ( J:142389 )

• spleen has 1.6-fold fewer B cells than controls

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:142389

Allelic Composition	Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺
Genetic Background	involves: 129P2/OlaHsd * BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igh-J^{tm2(3H9-VDJ*)Mwg} mutation (3 available); any Igh-J mutation (13 available)

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

immune system

abnormal B cell receptor editing ( J:131138 )

• despite the presence of a transgene that predisposes formation of DNA-binding antibodies, 70% of B cells do not produce anti-DNA antibodies because the transgene is edited or associates with a light chain that prevents DNA binding

• some B cells pair the transgenic heavy chain with an "editor" kappa light chain that prevents binding to DNA

• other B cells have recombination events of the transgenic heavy chain

• finally, there are non-responsive B cells that have dual expression of kappa and lambda light chains that make up to 30% of splenic B cells in older mice

abnormal marginal zone B cell morphology ( J:131138 )

• B cells that have dual expression of kappa and lambda light chains are sequestered in the marginal zone of the spleen that make up to 30% of splenic B cells in older mice

• these B cells have receptors that bind DNA but are unresponsive and do not secrete auto-antibodies

increased anti-double stranded DNA antibody level ( J:131138 )

• significant levels of anti-dsDNA IgM antibodies are seen in mice 6-8 weeks of age

• levels of these auto antibodies fall with age but are still detectable in some mice at 12 weeks of age

• no IgG anti-dsDNA antibodies are observed

hematopoietic system

abnormal B cell receptor editing ( J:131138 )

• some B cells pair the transgenic heavy chain with an "editor" kappa light chain that prevents binding to DNA

• other B cells have recombination events of the transgenic heavy chain

• finally, there are non-responsive B cells that have dual expression of kappa and lambda light chains that make up to 30% of splenic B cells in older mice

abnormal marginal zone B cell morphology ( J:131138 )

• B cells that have dual expression of kappa and lambda light chains are sequestered in the marginal zone of the spleen that make up to 30% of splenic B cells in older mice

• these B cells have receptors that bind DNA but are unresponsive and do not secrete auto-antibodies

Allelic Composition	Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺
Genetic Background	involves: 129P2/OlaHsd * BALB/c * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igh-J^{tm2(3H9-VDJ*)Mwg} mutation (3 available); any Igh-J mutation (13 available)

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

immune system

abnormal B cell receptor editing ( J:126940 )

• the heavy chain encoded by the knocked-in allele is paired with a very limited repertoire of kappa light chains with the majority of these being from the Vkappa21D family

• many of these kappa light chains disrupt the intrinsic DNA-binding ability of the heavy chain so that few B cells outside the bone marrow produce antibodies that bind double-stranded DNA

• sequence analysis reveals most B cells have undergone receptor rearrangement multiple times with a bias towards Jkappa5 occurring, deletion of Ckappa often observed, and a high frequency of deletional and inverted rearrangements

increased anti-double stranded DNA antibody level ( J:126940 )

• B cell hybridomas developed from these mice produce antibodies that bind dsDNA

hematopoietic system

abnormal B cell receptor editing ( J:126940 )

• the heavy chain encoded by the knocked-in allele is paired with a very limited repertoire of kappa light chains with the majority of these being from the Vkappa21D family

• many of these kappa light chains disrupt the intrinsic DNA-binding ability of the heavy chain so that few B cells outside the bone marrow produce antibodies that bind double-stranded DNA

Allelic Composition	Tcrb^tm1Mom/Tcrb^tm1Mom Tcrd^tm1Mom/Tcrd^tm1Mom Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺
Genetic Background	B6.129P2-Tcrb^tm1Mom Igh-J^{tm2(3H9-VDJ*)Mwg} Tcrd^tm1Mom

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igh-J^{tm2(3H9-VDJ*)Mwg} mutation (3 available); any Igh-J mutation (13 available)
Tcrb^tm1Mom mutation (12 available); any Tcrb mutation (97 available)
Tcrd^tm1Mom mutation (13 available); any Tcrd mutation (16 available)

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

immune system

increased marginal zone B cell number ( J:142389 )

• relative numbers of marginal B cells is increased more than 3-fold compared to wild-type controls

spleen hypoplasia ( J:142389 )

• spleen has 1.9- to 2.9- fold fewer spleen cells than controls

increased anti-double stranded DNA antibody level ( J:142389 )

• anti-dsDNA antibodies of the IgG2a isotype are detected in the sera of mice from 1 to 3 months of age

• anti-dsDNA antibodies with IgM, IgG2b, IgG3 isotypes are also present with levels of IgG3 extremly high compared to controls

• at 3 months of age, levels are higher than those found in 56R mice that have peripheral T cells

hematopoietic system

increased marginal zone B cell number ( J:142389 )

• relative numbers of marginal B cells is increased more than 3-fold compared to wild-type controls

spleen hypoplasia ( J:142389 )

• spleen has 1.9- to 2.9- fold fewer spleen cells than controls

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:142389

Allelic Composition	Cd4^tm1Mak/Cd4^tm1Mak Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺
Genetic Background	B6.Cg-Cd4^tm1Mak Igh-J^{tm2(3H9-VDJ*)Mwg}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd4^tm1Mak mutation (5 available); any Cd4 mutation (85 available)
Igh-J^{tm2(3H9-VDJ*)Mwg} mutation (3 available); any Igh-J mutation (13 available)

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

immune system

increased anti-double stranded DNA antibody level ( J:142389 )

• anti-dsDNA antibodies of IgG2a isotype are detected in the sera of mice at levels slightly less than that of 56R mice that have CD4 T cells present

• anti-dsDNA antibodies with IgM, IgG2b, IgG3 are also present in mice at 6 months of age though at levels less than those found in 56R mice with CD4 T cells

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:142389

Allelic Composition	Fas^lpr/Fas^lpr Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺
Genetic Background	MRL.Cg-Fas^lpr Igh-J^{tm2(3H9-VDJ*)Mwg}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fas^lpr mutation (39 available); any Fas mutation (82 available)
Igh-J^{tm2(3H9-VDJ*)Mwg} mutation (3 available); any Igh-J mutation (13 available)

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

immune system

abnormal B cell receptor editing ( J:131138 )

• Anti-dsDNA B cells have their transgenic heavy chains paired with kappa light chains that do not prevent DNA binding

• most anti-dsDNA B cells have also edited the heavy chain transgene suggesting de novo development of anti-DNA binding activity

• there is a decrease in the number of unresponsive B cells that express both lamda and kappa chains compared to transgenic mice on a BALB/c background (7.6% of splenic B cells versus to 19.4% )

abnormal marginal zone B cell morphology ( J:131138 )

• mice have a smaller marginal zone B cell population (3.4% of splenic lymphocytes) compared to MRL/lpr mice without the transgene (10.8%)

increased anti-double stranded DNA antibody level ( J:131138 )

• significant levels of IgM and IgG antibodies that bind dsDNA antibodies are detected in mice 6-8 weeks of age

• levels of these auto antibodies rise with age

• the levels of IgG are higher than in age-matched MRL/lpr mice that do not carry the transgene

hematopoietic system

abnormal B cell receptor editing ( J:131138 )

• Anti-dsDNA B cells have their transgenic heavy chains paired with kappa light chains that do not prevent DNA binding

• most anti-dsDNA B cells have also edited the heavy chain transgene suggesting de novo development of anti-DNA binding activity

• there is a decrease in the number of unresponsive B cells that express both lamda and kappa chains compared to transgenic mice on a BALB/c background (7.6% of splenic B cells versus to 19.4% )

abnormal marginal zone B cell morphology ( J:131138 )

• mice have a smaller marginal zone B cell population (3.4% of splenic lymphocytes) compared to MRL/lpr mice without the transgene (10.8%)

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:131138

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