Phenotypes associated with this allele

• Allele Symbol: Tnfrsf9^tm1Byk
• Allele Name: targeted mutation 1, Byoung Kwon
• Allele ID: MGI:2664914
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk	B6.Cg-Tnfrsf9^tm1Byk	MGI:2664915
hm2	Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk	C.Cg-Tnfrsf9^tm1Byk	MGI:4441173
cx3	Cd28^tm1Pjl/Cd28^tm1Pjl Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk	either: B6.Cg-Cd28^tm1Pjl Tnfrsf9^tm1Byk or C.Cg-Cd28^tm1Pjl Tnfrsf9^tm1Byk	MGI:2664937
cx4	Fas^lpr/Fas^lpr Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk	MRL.Cg-Tnfrsf9^tm1Byk Fas^lpr	MGI:3800222

Genotype
MGI:2664915

hm1

• Allelic Composition: Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk
• Genetic Background: B6.Cg-Tnfrsf9^tm1Byk

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

hematopoietic system

increased T cell proliferation ( J:83996 )

• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA

abnormal common myeloid progenitor cell morphology ( J:83996 )

• absolute numbers of granulocyte-macrophage, erythroid, and multipotential progenitor cells in the bone marrow, blood, and spleen are higher in mutants than wild-type mice

decreased IgG2a level ( J:83996 )

• 2-3-fold decrease in IgG2a in response to keyhole limpet hemocyanin (KLH) immunization

decreased IgG3 level ( J:83996 )

• 2-3-fold decrease in IgG3 in response to KLH immunization

abnormal cytotoxic T cell physiology ( J:83996 )

• mutants show significantly decreased cytotoxic T lymphocyte activity to vesicular stomatitis virus

immune system

increased T cell proliferation ( J:83996 )

• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA

decreased IgG2a level ( J:83996 )

• 2-3-fold decrease in IgG2a in response to keyhole limpet hemocyanin (KLH) immunization

decreased IgG3 level ( J:83996 )

• 2-3-fold decrease in IgG3 in response to KLH immunization

abnormal cytotoxic T cell physiology ( J:83996 )

• mutants show significantly decreased cytotoxic T lymphocyte activity to vesicular stomatitis virus

decreased interferon-gamma secretion ( J:83996 )

• decrease in IFN-gamma production in response to KLH immunization

• moderate decrease in IFN-gamma secretion from T cells

decreased interleukin-2 secretion ( J:83996 )

• moderate decrease in IL-2 secretion from T cells

decreased interleukin-4 secretion ( J:83996 )

• significant decrease in IL-4 secretion from T cells

cellular

increased T cell proliferation ( J:83996 )

• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA

Genotype
MGI:4441173

hm2

• Allelic Composition: Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk
• Genetic Background: C.Cg-Tnfrsf9^tm1Byk

hematopoietic system

increased T cell proliferation ( J:83996 )

• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA

increased splenocyte proliferation ( J:83722 )

• splenocytes show increased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA

abnormal common myeloid progenitor cell morphology ( J:83996 )

• absolute numbers of granulocyte-macrophage, erythroid, and multipotential progenitor cells in the bone marrow, blood, and spleen are higher in mutants than wild-type mice

abnormal immunoglobulin level ( J:83996 )

increased IgA level ( J:83722 )

• in naive mice

decreased IgG2a level ( J:83996 )

• 2-3-fold decrease in IgG2a in response to keyhole limpet hemocyanin (KLH) immunization

increased IgG2a level ( J:83722 )

• in naive mice

increased IgG2b level ( J:83722 )

• in naive mice

decreased IgG3 level ( J:83996 )

• 2-3-fold decrease in IgG3 in response to KLH immunization

abnormal cytotoxic T cell physiology ( J:83722 )

• Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability is reduced

immune system

increased T cell proliferation ( J:83996 )

• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA

increased splenocyte proliferation ( J:83722 )

• splenocytes show increased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA

abnormal immunoglobulin level ( J:83996 )

increased IgA level ( J:83722 )

• in naive mice

decreased IgG2a level ( J:83996 )

• 2-3-fold decrease in IgG2a in response to keyhole limpet hemocyanin (KLH) immunization

increased IgG2a level ( J:83722 )

• in naive mice

increased IgG2b level ( J:83722 )

• in naive mice

decreased IgG3 level ( J:83996 )

• 2-3-fold decrease in IgG3 in response to KLH immunization

abnormal cytotoxic T cell physiology ( J:83722 )

• Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability is reduced

decreased interferon-gamma secretion ( J:83996 )

• decrease in IFN-gamma production in response to KLH immunization

• moderate decrease in IFN-gamma secretion from T cells

decreased interleukin-12 secretion ( J:83722 )

• following ConA stimulation

decreased interleukin-2 secretion ( J:83996 )

• moderate decrease in IL-2 secretion from T cells

decreased interleukin-4 secretion ( J:83996 )

• significant decrease in IL-4 secretion from T cells

cellular

increased T cell proliferation ( J:83996 )

• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA

increased splenocyte proliferation ( J:83722 )

• splenocytes show increased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA

Genotype
MGI:2664937

cx3

• Allelic Composition: Cd28^tm1Pjl/Cd28^tm1Pjl; Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk
• Genetic Background: either: B6.Cg-Cd28^tm1Pjl Tnfrsf9^tm1Byk or C.Cg-Cd28^tm1Pjl Tnfrsf9^tm1Byk

immune system

decreased splenocyte proliferation ( J:83722 )

• splenocytes show decreased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA

abnormal class switch recombination ( J:83722 )

• mutants are incapable of undergoing Ig class switch and fail to mount anti-DNP responses of IgG1, IgG2a and IgM

decreased IgG1 level ( J:83722 )

• naive mutants exhibit decreased IgG1 levels and fail to mount anti-DNP responses of IgG1

decreased IgG2a level ( J:83722 )

• naive mutants exhibit decreased IgG2a levels and fail to mount anti-DNP responses of IgG2a

decreased IgM level ( J:83722 )

• mutants fail to mount anti-DNP responses of IgM and secrete reduced levels of IgM in response to a TD-antigen

abnormal cytotoxic T cell physiology ( J:83722 )

• Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability is reduced

decreased susceptibility to type IV hypersensitivity reaction ( J:83722 )

• mutants exhibit significantly suppressed contact hypersensitivity to FITC and DNFB

decreased interleukin-12 secretion ( J:83722 )

• following ConA stimulation

hematopoietic system

decreased splenocyte proliferation ( J:83722 )

• splenocytes show decreased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA

abnormal class switch recombination ( J:83722 )

• mutants are incapable of undergoing Ig class switch and fail to mount anti-DNP responses of IgG1, IgG2a and IgM

decreased IgG1 level ( J:83722 )

• naive mutants exhibit decreased IgG1 levels and fail to mount anti-DNP responses of IgG1

decreased IgG2a level ( J:83722 )

• naive mutants exhibit decreased IgG2a levels and fail to mount anti-DNP responses of IgG2a

decreased IgM level ( J:83722 )

• mutants fail to mount anti-DNP responses of IgM and secrete reduced levels of IgM in response to a TD-antigen

abnormal cytotoxic T cell physiology ( J:83722 )

• Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability is reduced

cellular

decreased splenocyte proliferation ( J:83722 )

• splenocytes show decreased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA

Genotype
MGI:3800222

cx4

• Allelic Composition: Fas^lpr/Fas^lpr; Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk
• Genetic Background: MRL.Cg-Tnfrsf9^tm1Byk Fas^lpr

cellular

increased lacrimal gland apoptosis ( J:126929 )

• more apoptotic cells are detected relative to wild-type Tnfrsf9, Fas ^lpr controls

mortality/aging

premature death ( J:127197 )

• by 5 months, 80% mortality is observed compared to 40% in Tnfrsf9-sufficient, Fas-null mice; by 4 months, mice become increasingly moribund and display reduced activity

hematopoietic system

hematopoietic system phenotype ( J:127197 )

N • CD8beta+ T cells are not altered in number at any age

enlarged spleen ( J:127197 )

• significant enlargement of axillary lymph nodes is seen at 5 months compared to Tnfrsf9-wt, Fas-null mice

increased double-negative T cell number ( J:126929 , J:127197 )

• in lacrimal glands, DN T cell percentages are about 2-fold greater than in wild-type Tnfrsf9, Fas ^lpr controls; similar increases are seen in spleen and salivary glands (J:126929)

• increased proportion seen in spleen compared to Tnfrsf9-sufficient, Fas-null mice (J:127197)

increased B-1 B cell number ( J:127197 )

• percentages of B-1 (B220+ CD5+) cells are increased significantly in peritoneums and slightly higher in spleens

increased B-2 B cell number ( J:127197 )

• percentages of B-2( B220+ CD5-) cells are increased significantly in peritoneums and slightly higher in spleens

increased CD4-positive, alpha-beta T cell number ( J:126929 , J:127197 )

• 3- and 5-month old mice show elevated CD4+ T cell numbers in lacrimal glands (J:126929)

• mice display early increases in CD4+ T cells in spleen, and numbers keep rising (J:127197)

increased spleen germinal center number ( J:127197 )

• greatly increased germinal center formation is observed compared to Tnfrsf9-sufficient, Fas-null mice

increased immunoglobulin level ( J:127197 )

• circulating titres are elevated compared with compared to Tnfrsf9-sufficient, Fas-null mice

immune system

lacrimal gland inflammation ( J:126929 )

• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas ^lpr homozygotes

• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age

enlarged spleen ( J:127197 )

• significant enlargement of axillary lymph nodes is seen at 5 months compared to Tnfrsf9-wt, Fas-null mice

increased double-negative T cell number ( J:126929 , J:127197 )

• in lacrimal glands, DN T cell percentages are about 2-fold greater than in wild-type Tnfrsf9, Fas ^lpr controls; similar increases are seen in spleen and salivary glands (J:126929)

• increased proportion seen in spleen compared to Tnfrsf9-sufficient, Fas-null mice (J:127197)

increased B-1 B cell number ( J:127197 )

• percentages of B-1 (B220+ CD5+) cells are increased significantly in peritoneums and slightly higher in spleens

increased B-2 B cell number ( J:127197 )

• percentages of B-2( B220+ CD5-) cells are increased significantly in peritoneums and slightly higher in spleens

increased CD4-positive, alpha-beta T cell number ( J:126929 , J:127197 )

• 3- and 5-month old mice show elevated CD4+ T cell numbers in lacrimal glands (J:126929)

• mice display early increases in CD4+ T cells in spleen, and numbers keep rising (J:127197)

increased spleen germinal center number ( J:127197 )

• greatly increased germinal center formation is observed compared to Tnfrsf9-sufficient, Fas-null mice

increased immunoglobulin level ( J:127197 )

• circulating titres are elevated compared with compared to Tnfrsf9-sufficient, Fas-null mice

enlarged lymph nodes ( J:127197 )

• significant enlargement at 5 months compared to Tnfrsf9-wt, Fas-null mice

increased interleukin-4 secretion ( J:126929 )

• in lacrimal glands, increased levels of Il-4 are detected compared to controls

increased susceptibility to systemic lupus erythematosus ( J:127197 )

• phenotypic manifestations are increased relative to Fas^lpr homozygotes

increased anti-nuclear antigen antibody level ( J:127197 )

• serum titres of anti-nuclear IgG1/2a are increased at 3 and 5 months

• anti-DNA antibody production is increased compared to Tnfrsf9-sufficient, Fas-null mice

renal/urinary system

abnormal kidney morphology ( J:126929 )

• increased immunoglobulin deposits are detected in kidneys compared to controls

cortical renal glomerulopathies ( J:127197 )

• mice show exacerbated renal injury, with increased glomerular infiltrates

renal glomerular protein deposits ( J:127197 )

• IgG and C3 depositions in kidneys are increased compared with Tnfrsf9-sufficient, Fas-null mice

craniofacial

abnormal outer ear morphology ( J:127197 )

• from 4 months of age, >60% of mice display progressive erosion of pinnae

hearing/vestibular/ear

abnormal outer ear morphology ( J:127197 )

• from 4 months of age, >60% of mice display progressive erosion of pinnae

endocrine/exocrine glands

increased lacrimal gland apoptosis ( J:126929 )

• more apoptotic cells are detected relative to wild-type Tnfrsf9, Fas ^lpr controls

abnormal lacrimal gland morphology ( J:126929 )

• increased deposits of IgG1, but not IgG2a are detected in lacrimal glands at 3 and 5 months

lacrimal gland inflammation ( J:126929 )

• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas ^lpr homozygotes

• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age

vision/eye

increased lacrimal gland apoptosis ( J:126929 )

• more apoptotic cells are detected relative to wild-type Tnfrsf9, Fas ^lpr controls

abnormal lacrimal gland morphology ( J:126929 )

• increased deposits of IgG1, but not IgG2a are detected in lacrimal glands at 3 and 5 months

lacrimal gland inflammation ( J:126929 )

• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas ^lpr homozygotes

• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age

integument

skin lesions ( J:127197 )

• by 5 months, skin lesions around tip of nose and around ears are more pronounced than in Tnfrsf9-wt, Fas-null mice

growth/size/body

abnormal outer ear morphology ( J:127197 )

• from 4 months of age, >60% of mice display progressive erosion of pinnae

enlarged spleen ( J:127197 )

• significant enlargement of axillary lymph nodes is seen at 5 months compared to Tnfrsf9-wt, Fas-null mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:120559
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:120559