Phenotypes associated with this allele

• Allele Symbol: Cd4^tm1Mak
• Allele Name: targeted mutation 1, Tak Mak
• Allele ID: MGI:1857144
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cd4^tm1Mak/Cd4^tm1Mak	B6.129S2-Cd4^tm1Mak/J	MGI:3809395
hm2	Cd4^tm1Mak/Cd4^tm1Mak	involves: 129S2/SvPas	MGI:3800775
hm3	Cd4^tm1Mak/Cd4^tm1Mak	involves: 129S2/SvPas * C57BL/6 * DBA/2	MGI:3052045
hm4	Cd4^tm1Mak/Cd4^tm1Mak	PL.129S2(B6)-Cd4^tm1Mak/Rdgz	MGI:3052046
hm5	Cd4^tm1Mak/Cd4^tm1Mak	SJL.129S2(B6)-Cd4^tm1Mak/Rdgz	MGI:3052047
cx6	Cd4^tm1Mak/Cd4^tm1Mak Igh-J^tm2(3H9-VDJ*)Mwg/Igh-J^+	B6.Cg-Cd4^tm1Mak Igh-J^tm2(3H9-VDJ*)Mwg	MGI:3836922
cx7	B2m^tm1Unc/B2m^tm1Unc Cd4^tm1Mak/Cd4^tm1Mak Cd8a^tm2.1(Cd4)Asin/Cd8a^tm2.1(Cd4)Asin	involves: 129 * C57BL/6	MGI:5309023
cx8	Cd4^tm1Mak/Cd4^tm1Mak Cd8a^tm1Mak/Cd8a^tm1Mak	involves: 129S2/SvPas	MGI:3800776
cx9	Cd4^tm1Mak/Cd4^tm1Mak Irf2^tm1Mak/Irf2^tm1Mak	involves: 129S2/SvPas * C57BL/6	MGI:3630270
cx10	Cd4^tm1Mak/Cd4^tm1Mak Cd8a^tm1Mak/Cd8a^tm1Mak	involves: 129S2/SvPas * C57BL/6 * DBA/2	MGI:3800764
cx11	Cd4^tm1Mak/Cd4^tm1Mak Tnf^tm2Gkl/Tnf^+	involves: 129S/SvEv * 129S2/SvPas * C57BL/6J	MGI:3629516

Genotype
MGI:3809395

hm1

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak
• Genetic Background: B6.129S2-Cd4^tm1Mak/J

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

immune system

immune system phenotype ( J:133047 )

N

absent plasma cells ( J:133047 )

hematopoietic system

absent plasma cells ( J:133047 )

homeostasis/metabolism

abnormal bile salt level ( J:133047 )

Genotype
MGI:3800775

hm2

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak
• Genetic Background: involves: 129S2/SvPas

immune system

immune system phenotype ( J:110749 )

N • mice clear polyomavirus within one month of infection similar to controls

Genotype
MGI:3052045

hm3

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA/2

hematopoietic system

increased CD8-positive, alpha-beta T cell number ( J:68957 )

• peripheral CD8+ cell population is expanded

abnormal CD4-positive, alpha-beta T cell physiology ( J:68957 )

• no response to class II alloantigens, but normal class I

immune system

increased CD8-positive, alpha-beta T cell number ( J:68957 )

• peripheral CD8+ cell population is expanded

abnormal CD4-positive, alpha-beta T cell physiology ( J:68957 )

• no response to class II alloantigens, but normal class I

increased susceptibility to Picornaviridae infection ( J:92227 )

• significantly increased inflammation in the first week of TMEV infection which is mostly resolved by 45 days after infection on the resistant C57BL/6 background

• persistent infectious virus at 45 days and increasing clinical symptoms over time

• at 10 months, 93% of mice present clinical symptoms on the resistant C57BL/6 background

nervous system

demyelination ( J:92227 )

• on the resistant C57BL/6 background, demyelination was light at 45 days after TMEV infection, but extensive at 90 days

Genotype
MGI:3052046

hm4

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak
• Genetic Background: PL.129S2(B6)-Cd4^tm1Mak/Rdgz

immune system

brain inflammation ( J:92227 )

• severely increased meningeal inflammation on both PL/J and SJL/J backgrounds after infection with TMEV

increased susceptibility to Picornaviridae infection ( J:92227 )

• inflammation persists in the susceptible PL/J background, particularly in the cerebellum, brainstem and striatum

nervous system

brain inflammation ( J:92227 )

• severely increased meningeal inflammation on both PL/J and SJL/J backgrounds after infection with TMEV

demyelination ( J:92227 )

• demyelination was severe on both the susceptible PL/J and SJL/J backgrounds after infection with TMEV

Genotype
MGI:3052047

hm5

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak
• Genetic Background: SJL.129S2(B6)-Cd4^tm1Mak/Rdgz

immune system

brain inflammation ( J:92227 )

• severely increased meningeal inflammation on both PL/J and SJL/J backgrounds after infection with TMEV

increased susceptibility to Picornaviridae infection ( J:92227 )

• inflammation persists in the susceptible SJL/J background, particularly in the cerebellum, brainstem and striatum

nervous system

brain inflammation ( J:92227 )

• severely increased meningeal inflammation on both PL/J and SJL/J backgrounds after infection with TMEV

demyelination ( J:92227 )

• demyelination was severe on both the susceptible PL/J and SJL/J backgrounds after infection with TMEV

Genotype
MGI:3836922

cx6

• 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}

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

Genotype
MGI:5309023

cx7

• Allelic Composition: B2m^tm1Unc/B2m^tm1Unc; Cd4^tm1Mak/Cd4^tm1Mak; Cd8a^{tm2.1(Cd4)Asin}/Cd8a^{tm2.1(Cd4)Asin}
• Genetic Background: involves: 129 * C57BL/6

immune system

abnormal T cell physiology ( J:180236 )

• lack of helper T cell function

• retain cytotoxic T cell functions

hematopoietic system

abnormal T cell physiology ( J:180236 )

• lack of helper T cell function

• retain cytotoxic T cell functions

Genotype
MGI:3800776

cx8

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak; Cd8a^tm1Mak/Cd8a^tm1Mak
• Genetic Background: involves: 129S2/SvPas

immune system

increased susceptibility to viral infection ( J:110749 )

• virus is still detectable in bone marrow, heart, and other organs 1 month after polyomavirus infection compared to controls that clear the infection by one month

Genotype
MGI:3630270

cx9

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak; Irf2^tm1Mak/Irf2^tm1Mak
• Genetic Background: involves: 129S2/SvPas * C57BL/6

integument

abnormal skin condition ( J:66034 )

• mice develop similar skin symptoms to Irf2-null mice

Genotype
MGI:3800764

cx10

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak; Cd8a^tm1Mak/Cd8a^tm1Mak
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA/2

immune system

small thymus medulla ( J:12572 )

• the medulla is reduced in size

abnormal T cell differentiation ( J:12572 )

• there is a 5-fold drop in the number of mature alphabeta TCR⁺ HAS^- T cells in the thymus

• alphabeta TCR expression on these mature double negative cells is lower than in mature T cells of wild-type mice

• despite lack of CD4 and CD8 expression, alphabeta T cells are still present in the periphery

abnormal double-negative T cell morphology ( J:12572 )

• "mature" double negative thymocytes are found that are alphabeta TCR⁺ HAS^-

decreased double-positive T cell number ( J:12572 )

• double positive T cells are absent

abnormal T cell number ( J:12572 )

• the alphabeta T cell number in lymph nodes varies from 5% to 50% of normal

abnormal gamma-delta T cell number ( J:12572 )

• the absolute number of gammadelta T cells is decreased though the relative percentage of lymph node is increased from 1% to 3%

decreased cytotoxic T cell cytolysis ( J:12572 )

• LCMV-specific class I MHC-restricted cytotoxic T cell responses are not activated in these mice

• alloantigen specific lysis of target cells by T cells in mixed lymphocyte culture is reduced

• the lysis of cells is specific for class I MHC antigens

increased length of allograft survival ( J:12572 )

• tail skin graphs from donor mice of the same MHC haplotypes are not rejected within a three month period compared to controls that have no graph survival after 18 days

• when donor mice have a different MHC haplotype, skin graft rejection is similar to controls

hematopoietic system

small thymus medulla ( J:12572 )

• the medulla is reduced in size

abnormal T cell differentiation ( J:12572 )

• there is a 5-fold drop in the number of mature alphabeta TCR⁺ HAS^- T cells in the thymus

• alphabeta TCR expression on these mature double negative cells is lower than in mature T cells of wild-type mice

• despite lack of CD4 and CD8 expression, alphabeta T cells are still present in the periphery

abnormal double-negative T cell morphology ( J:12572 )

• "mature" double negative thymocytes are found that are alphabeta TCR⁺ HAS^-

abnormal T cell number ( J:12572 )

• the alphabeta T cell number in lymph nodes varies from 5% to 50% of normal

decreased double-positive T cell number ( J:12572 )

• double positive T cells are absent

abnormal gamma-delta T cell number ( J:12572 )

• the absolute number of gammadelta T cells is decreased though the relative percentage of lymph node is increased from 1% to 3%

decreased cytotoxic T cell cytolysis ( J:12572 )

• LCMV-specific class I MHC-restricted cytotoxic T cell responses are not activated in these mice

• alloantigen specific lysis of target cells by T cells in mixed lymphocyte culture is reduced

• the lysis of cells is specific for class I MHC antigens

endocrine/exocrine glands

small thymus medulla ( J:12572 )

• the medulla is reduced in size

Genotype
MGI:3629516

cx11

• Allelic Composition: Cd4^tm1Mak/Cd4^tm1Mak; Tnf^tm2Gkl/Tnf⁺
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6J

mortality/aging

premature death ( J:108572 )

• there is high incidence of mortality in mice by age of 2-3 months

immune system

small intestinal inflammation ( J:108572 )

• mice show exacerbation of IBD compared to Tnf^tm2Gkl/+ mice

digestive/alimentary system

small intestinal inflammation ( J:108572 )

• mice show exacerbation of IBD compared to Tnf^tm2Gkl/+ mice