Phenotypes associated with this allele

• Allele Symbol: Ighm^tm1Msn
• Allele Name: targeted mutation 1, Michael S Neuberger
• Allele ID: MGI:2447178
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ighm^tm1Msn/Ighm^tm1Msn	B6.129S-Ighm^tm1Msn	MGI:3815444
hm2	Ighm^tm1Msn/Ighm^tm1Msn	involves: 129S/SvEv	MGI:3815407
hm3	Ighm^tm1Msn/Ighm^tm1Msn	involves: 129S/SvEv * C57BL/6	MGI:3815426
ht4	Ighm^tm1Msn/Ighm^+	involves: 129S/SvEv	MGI:3815406
cx5	Ighm^tm1Msn/Ighm^tm1Msn Tg(Igh-6)1Msn/?	B6.129S-Ighm^tm1Msn	MGI:3815445

Genotype
MGI:3815444

hm1

• Allelic Composition: Ighm^tm1Msn/Ighm^tm1Msn
• Genetic Background: B6.129S-Ighm^tm1Msn

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

immune system

decreased follicular B cell number ( J:80656 )

• there is a 25% reduction in the number of follicular B cells

increased marginal zone B cell number ( J:80656 )

• there is a 2.5-fold increase in the number of marginal zone CD21^highCD23^low B cells

• a larger IgM^brightIgD^dull MZ area on the periphery of the follicle exists compared with wild-type controls

• a reduction in MZ B cell number is observed after the administration of polyclonal IgM

abnormal B-1a B cell morphology ( J:80656 )

• there is a doubling in the number of CD5⁺B cells found in the spleen

• increased B-1a B cells are also found in the peritoneum

abnormal splenic cell ratio ( J:80656 )

• the ratio of marginal zone B cell numbers to follicular B cell numbers (MZ:FO) is more than double that of wild-type mice at 4 months of age

• at 12 months of age the MZ:FO ratio is not as elevated but is still significantly higher than age-matched controls

• this ratio can be normalized by administration of polyclonal, but not monoclonal, IgM

decreased IgM level ( J:80656 )

• serum levels of IgM are undetectable in these mice

hematopoietic system

decreased follicular B cell number ( J:80656 )

• there is a 25% reduction in the number of follicular B cells

increased marginal zone B cell number ( J:80656 )

• there is a 2.5-fold increase in the number of marginal zone CD21^highCD23^low B cells

• a larger IgM^brightIgD^dull MZ area on the periphery of the follicle exists compared with wild-type controls

• a reduction in MZ B cell number is observed after the administration of polyclonal IgM

abnormal B-1a B cell morphology ( J:80656 )

• there is a doubling in the number of CD5⁺B cells found in the spleen

• increased B-1a B cells are also found in the peritoneum

abnormal splenic cell ratio ( J:80656 )

• the ratio of marginal zone B cell numbers to follicular B cell numbers (MZ:FO) is more than double that of wild-type mice at 4 months of age

• at 12 months of age the MZ:FO ratio is not as elevated but is still significantly higher than age-matched controls

• this ratio can be normalized by administration of polyclonal, but not monoclonal, IgM

decreased IgM level ( J:80656 )

• serum levels of IgM are undetectable in these mice

Genotype
MGI:3815407

hm2

• Allelic Composition: Ighm^tm1Msn/Ighm^tm1Msn
• Genetic Background: involves: 129S/SvEv

immune system

abnormal immature B cell morphology ( J:49405 )

• B cells in the bone marrow have reduced surface expression of IgM

abnormal mature B cell morphology ( J:49405 )

• splenic B cells have enhanced surface expression of IgM and decreased expression of IgD

abnormal B-1a B cell morphology ( J:49405 )

• B-1a B cell population is expanded in the peritoneum

• 65% of the B220⁺peritoneal cells are CD51 compared with 38% of B cells in controls

decreased IgG1 level ( J:49405 )

• after injection of a T cell-dependent antigen, mice have a 5-fold reduction in serum levels of antigen-specific IgG1 compared to controls

• the affinity of the IgG1 antibodies to antigen is lower than wild-type

• this defect could be rescued by the co-administration of IgM collected from the sera of non-immunized mice

• mice are also able to increase titers of IgG1 upon administration of a booster, to levels similar to that of wild-type mice

increased IgG3 level ( J:49405 )

• when mice are immunized with a T cell-independent antigen, serum levels of IgG3 are enhanced 3-fold compared to controls

• levels of other IgG levels are augmented also though specifics are not given

decreased IgM level ( J:49405 )

• IgM serum levels are undetectable

hematopoietic system

abnormal immature B cell morphology ( J:49405 )

• B cells in the bone marrow have reduced surface expression of IgM

abnormal mature B cell morphology ( J:49405 )

• splenic B cells have enhanced surface expression of IgM and decreased expression of IgD

abnormal B-1a B cell morphology ( J:49405 )

• B-1a B cell population is expanded in the peritoneum

• 65% of the B220⁺peritoneal cells are CD51 compared with 38% of B cells in controls

decreased IgG1 level ( J:49405 )

• after injection of a T cell-dependent antigen, mice have a 5-fold reduction in serum levels of antigen-specific IgG1 compared to controls

• the affinity of the IgG1 antibodies to antigen is lower than wild-type

• this defect could be rescued by the co-administration of IgM collected from the sera of non-immunized mice

• mice are also able to increase titers of IgG1 upon administration of a booster, to levels similar to that of wild-type mice

increased IgG3 level ( J:49405 )

• when mice are immunized with a T cell-independent antigen, serum levels of IgG3 are enhanced 3-fold compared to controls

• levels of other IgG levels are augmented also though specifics are not given

decreased IgM level ( J:49405 )

• IgM serum levels are undetectable

Genotype
MGI:3815426

hm3

• Allelic Composition: Ighm^tm1Msn/Ighm^tm1Msn
• Genetic Background: involves: 129S/SvEv * C57BL/6

immune system

increased autoantibody level ( J:111817 )

• about one-third to one-half of mice between 12-18 months of age have auto-antibodies to cardiolipin, myeloperoxidase, and/or dsDNA

increased anti-double stranded DNA antibody level ( J:111817 )

• about one-third of mice between 12-18 months of age have elevated levels of anti-dsDNA IgG antibodies

• these levels are three standard error of means over levels found in age-matched controls

• anti-dsDNA antibodies are also found in 3-month old mice that have been repeatedly injected with LPS while none are found in controls

kidney inflammation ( J:111817 )

• 1 mouse of 13 has overt nephritis

• 6 of 13 mice have high levels of IgG and/or C3 deposition in the kidney

renal/urinary system

kidney inflammation ( J:111817 )

• 1 mouse of 13 has overt nephritis

• 6 of 13 mice have high levels of IgG and/or C3 deposition in the kidney

Genotype
MGI:3815406

ht4

• Allelic Composition: Ighm^tm1Msn/Ighm⁺
• Genetic Background: involves: 129S/SvEv

immune system

decreased IgM level ( J:49405 )

• IgM serum levels are reduced by 50%

hematopoietic system

decreased IgM level ( J:49405 )

• IgM serum levels are reduced by 50%

Genotype
MGI:3815445

cx5

• Allelic Composition: Ighm^tm1Msn/Ighm^tm1Msn; Tg(Igh-6)1Msn/?
• Genetic Background: B6.129S-Ighm^tm1Msn

immune system

decreased follicular B cell number ( J:80656 )

• there is a 25% reduction in the number of follicular B cells

increased marginal zone B cell number ( J:80656 )

• there is a 2.5-fold increase in the number of marginal zone CD21^highCD23^low B cells

• a larger IgM^brightIgD^dull MZ area on the periphery of the follicle compared with wild-type controls

abnormal B-1a B cell morphology ( J:80656 )

• there is a doubling in the number of CD5⁺B cells found in the spleen

• increased B-1a B cells are also found in the peritoneum

abnormal splenic cell ratio ( J:80656 )

• the ratio of marginal zone B cell numbers to follicular B cell numbers (MZ:FO) is more than double that of wild-type mice at 4 months of age

• at 12 months of age the MZ:FO ratio is not as elevated but is still significantly higher than age-matched controls

decreased IgM level ( J:80656 )

• serum levels of IgM are undetectable in these mice

hematopoietic system

decreased follicular B cell number ( J:80656 )

• there is a 25% reduction in the number of follicular B cells

increased marginal zone B cell number ( J:80656 )

• there is a 2.5-fold increase in the number of marginal zone CD21^highCD23^low B cells

• a larger IgM^brightIgD^dull MZ area on the periphery of the follicle compared with wild-type controls

abnormal B-1a B cell morphology ( J:80656 )

• there is a doubling in the number of CD5⁺B cells found in the spleen

• increased B-1a B cells are also found in the peritoneum

abnormal splenic cell ratio ( J:80656 )

• the ratio of marginal zone B cell numbers to follicular B cell numbers (MZ:FO) is more than double that of wild-type mice at 4 months of age

• at 12 months of age the MZ:FO ratio is not as elevated but is still significantly higher than age-matched controls

decreased IgM level ( J:80656 )

• serum levels of IgM are undetectable in these mice