Mouse Genome Informatics
hm1
    H2b/H2b
NOD.B10SnJ-H2b
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• no female mice homozygous for this haplotype develop diabetes after cyclophosphamide injections during 5-13 months of observation

endocrine/exocrine glands
• female mice display spontaneous perivascular and periductal lymphocytic infiltration by 7-10 months of age; mice between 6 and 11 months of age that are treated with cyclophospamide display perivascular and periductal infiltrates

immune system
• female mice display spontaneous perivascular and periductal lymphocytic infiltration by 7-10 months of age; mice between 6 and 11 months of age that are treated with cyclophospamide display perivascular and periductal infiltrates
• no female mice homozygous for the haplotype develop diabetes spontaneously during 5-13 months of observation


Mouse Genome Informatics
ht2
    H2b/H2d
(C57BL/6 x DBA/2)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• after malarial infection, large populations of B220+CD3+ cells which are extrathymic T cells (CD3+) carrying a B cell marker (B220+) appear in the livers; this is not seen in the spleens of any mice after infection
• there is an increase of 40% of gamma,delta T cells in DBA/2 mice during infection; most of these are CD4-CD8-
• levels of Ifng and Il4 are lower than in B6 mice with malarial infection
• level of IgM autoantibody is increase to a greater extent than in B6 mice
• recovery from malaria is similar to DBA/2 mice, faster than in B6 mice

hematopoietic system
• decrease in hematocrit is less than in infected C57BL/6 mice
• after malarial infection, large populations of B220+CD3+ cells which are extrathymic T cells (CD3+) carrying a B cell marker (B220+) appear in the livers; this is not seen in the spleens of any mice after infection
• there is an increase of 40% of gamma,delta T cells in DBA/2 mice during infection; most of these are CD4-CD8-

liver/biliary system
• liver injury as estimated by GPT serum levels is lower than in infected B6 mice


Mouse Genome Informatics
ht3
    H2b/H2g7
NOD.B10SnJ-H2b
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• no females develop diabetes spontaneously over 5-7 months


Mouse Genome Informatics
cx4
    H2b/H2b
Ptcratm1Vbo/Ptcratm1Vbo

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• thymocyte number is decreased by 10-fold compared to controls
• the percentage of DP thymocytes is severely reduced in the thymocytes
• spleen numbers are reduced by more than 4-fold

immune system
• thymocyte number is decreased by 10-fold compared to controls
• the percentage of DP thymocytes is severely reduced in the thymocytes
• spleen numbers are reduced by more than 4-fold

endocrine/exocrine glands
• thymocyte number is decreased by 10-fold compared to controls


Mouse Genome Informatics
cx5
    H2b/H2b
Tcratm1Mom/Tcra/Tcrdtm1.1(Tcra)Rsky
Tg(Tcrb)93Vbo/?

involves: 129P2/OlaHsd * C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• thymocyte number is reduced by about half compared to controls
• 18% of lymph node T cells from female mice bearing H2-Db express the HY-alpha t cell receptor chain
• the majority of T cells in male mice are HYalpha+ CD4-CD8lo or HYalpha+ CD4-CD8-
• 5 of 29 thymocytes from H2-Db background mice not expressing the HY TCR show evidence of receptor editing though the small number of DP and SP thymocytes present suggests this process is inefficient
• thymocytes from male mice on a H2-Db background that express the HY receptor are CD69+ and undergoing apoptosis due to negative selection
• DN thymocytes of both sexes have premature expression of a T cell receptor (TCR)
• this TCR is specific for the male HY antigen and in many cases there is co-expression of CD25 and CD44
• the percentage of DN cells in the thymus is increased
• female mice on a H2-Db background have almost double the number of DP thymocytes compared to female mice carrying just the Tcrbeta transgene
• the majority of these DP thymocytes do not carry the HY TCR
• male mice on a H2-Db background have 4% the number of double positive thymocytes
• the percentage of DP thymocytes is decreased in these mice

hematopoietic system
• thymocyte number is reduced by about half compared to controls
• 18% of lymph node T cells from female mice bearing H2-Db express the HY-alpha t cell receptor chain
• the majority of T cells in male mice are HYalpha+ CD4-CD8lo or HYalpha+ CD4-CD8-
• 5 of 29 thymocytes from H2-Db background mice not expressing the HY TCR show evidence of receptor editing though the small number of DP and SP thymocytes present suggests this process is inefficient
• thymocytes from male mice on a H2-Db background that express the HY receptor are CD69+ and undergoing apoptosis due to negative selection
• DN thymocytes of both sexes have premature expression of a T cell receptor (TCR)
• this TCR is specific for the male HY antigen and in many cases there is co-expression of CD25 and CD44
• the percentage of DN cells in the thymus is increased
• female mice on a H2-Db background have almost double the number of DP thymocytes compared to female mice carrying just the Tcrbeta transgene
• the majority of these DP thymocytes do not carry the HY TCR
• male mice on a H2-Db background have 4% the number of double positive thymocytes
• the percentage of DP thymocytes is decreased in these mice

endocrine/exocrine glands
• thymocyte number is reduced by about half compared to controls


Mouse Genome Informatics
cx6
    Tcratm1Mom/Tcra/Tcrdtm1.1(Tcra)Rsky
H2b/H2b
Tg(Tcrb)93Vbo/?

involves: 129P2/OlaHsd * C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• 18% of lymph node T cells from female mice bearing H2-Db express the HY-alpha t cell receptor chain
• the majority of T cells in male mice are HYalpha+ CD4-CD8lo or HYalpha+ CD4-CD8-
• 5 of 29 HY- thymocytes from H2-Db background mice have some receptor editing though the small number of DP and SP thymocytes present suggests this process is inefficient
• thymocytes from male mice on a H2-Db background that express the HY receptor are CD69+ and undergoing apoptosis due to negative selection
• DN thymocytes of both sexes have premature expression of a T cell receptor (TCR)
• this TCR is specific for the male HY antigen and in many cases there is co-expression of CD25 and CD44
• the percentage of DN cells in the thymus is increased
• female mice on a H2-Db background have almost double the number of DP thymocytes compared to female mice carrying just the Tcrbeta transgene
• the majority of these DP thymocytes do not carry the HY TCR
• male mice on a H2-Db background have 4% the number of double positive thymocytes

immune system
• 18% of lymph node T cells from female mice bearing H2-Db express the HY-alpha t cell receptor chain
• the majority of T cells in male mice are HYalpha+ CD4-CD8lo or HYalpha+ CD4-CD8-
• 5 of 29 HY- thymocytes from H2-Db background mice have some receptor editing though the small number of DP and SP thymocytes present suggests this process is inefficient
• thymocytes from male mice on a H2-Db background that express the HY receptor are CD69+ and undergoing apoptosis due to negative selection
• DN thymocytes of both sexes have premature expression of a T cell receptor (TCR)
• this TCR is specific for the male HY antigen and in many cases there is co-expression of CD25 and CD44
• the percentage of DN cells in the thymus is increased
• female mice on a H2-Db background have almost double the number of DP thymocytes compared to female mice carrying just the Tcrbeta transgene
• the majority of these DP thymocytes do not carry the HY TCR
• male mice on a H2-Db background have 4% the number of double positive thymocytes

endocrine/exocrine glands


Mouse Genome Informatics
cx7
    H2b/H2b
Tcra/Tcrdtm1.1(Tcra)Rsky/Tcra/Tcrdtm1.1(Tcra)Rsky
Tg(Tcrb)93Vbo/?

involves: 129P2/OlaHsd * C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• male mice on a H2-Db background have no distinct double positive or double negative populations in their thymus
• almost all thymocytes in male mice on a H2-Db background undergo negative selection
• receptor editing is unable to rescue these thymocytes

hematopoietic system
• male mice on a H2-Db background have no distinct double positive or double negative populations in their thymus
• almost all thymocytes in male mice on a H2-Db background undergo negative selection
• receptor editing is unable to rescue these thymocytes


Mouse Genome Informatics
cx8
    H2b/H2b
Tcra/Tcrdtm1.1(Tcra)Rsky/Tcra/Tcrdtm1.1(Tcra)Rsky
Tg(Tcrb)93Vbo/?

involves: 129P2/OlaHsd * C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• male mice on a H2-Db background have no distinct double positive or double negative populations in their thymus
• receptor editing is unable to rescue these thymocytes
• almost all thymocytes in male mice on a H2-Db background undergo negative selection

immune system
• male mice on a H2-Db background have no distinct double positive or double negative populations in their thymus
• almost all thymocytes in male mice on a H2-Db background undergo negative selection
• receptor editing is unable to rescue these thymocytes


Mouse Genome Informatics
cx9
    H2b/H2b
Ptcratm1Vbo/Ptcratm1Vbo
Tcratm1Mom/Tcra/Tcrdtm1.1(Tcra)Rsky
Tg(Tcrb)93Vbo/?

involves: 129P2/OlaHsd * C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• thymocyte numbers are reduced by about 3-fold
• the presence of HY TCR alleviates the beta-selection block in Ptcratm1Vbo homozygotes with higher T cell numbers being found in the thymus and the spleen
• despite the increased numbers of thymocytes, the CD25+ thymocyte sub-population still remains very low

hematopoietic system
• thymocyte numbers are reduced by about 3-fold
• the presence of HY TCR alleviates the beta-selection block in Ptcratm1Vbo homozygotes with higher T cell numbers being found in the thymus and the spleen
• despite the increased numbers of thymocytes, the CD25+ thymocyte sub-population still remains very low

endocrine/exocrine glands
• thymocyte numbers are reduced by about 3-fold


Mouse Genome Informatics
cx10
    H2b/H2b
Ptcratm1Vbo/Ptcratm1Vbo
Tg(TcraH-Y,TcrbH-Y)71Vbo/?

involves: 129P2/OlaHsd * C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the presence of HY TCR alleviates the beta-selection block of developing T cells found in Ptcratm1Vbo homozygotes resulting in higher T cell numbers being found in the thymus and the spleen
• the presence of the selecting H2d allele contributes to the rescue of T cell development by the HY-TCR
• despite the increased numbers of thymocytes, the CD25+ thymocyte sub-population still remains very low

hematopoietic system
• the presence of HY TCR alleviates the beta-selection block of developing T cells found in Ptcratm1Vbo homozygotes resulting in higher T cell numbers being found in the thymus and the spleen
• the presence of the selecting H2d allele contributes to the rescue of T cell development by the HY-TCR
• despite the increased numbers of thymocytes, the CD25+ thymocyte sub-population still remains very low


Mouse Genome Informatics
cx11
    H2b/H2b
Nfkbidtm1Clay/Nfkbidtm1Clay
Rag2tm1Fwa/Rag2tm1Fwa
Tg(TcraN15,TcrbN15)L2Elre/?

involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• thymocytes proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
• T cells proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
• T cells require about 2 logs higher concentration of antigen for proliferation equivalent of wild-type T cells
• lymph node T cells secrete significantly less IL-2 than wild-type T cells in response to irradiated spleen cells loaded with VSV8 antigen

hematopoietic system
• thymocytes proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
• T cells proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen
• T cells require about 2 logs higher concentration of antigen for proliferation equivalent of wild-type T cells

endocrine/exocrine glands
• thymocytes proliferate poorly to irradiated, wild-type spleen cells loaded with VSV8 antigen


Mouse Genome Informatics
cx12
    H2b/H2b
Rag2tm1Fwa/Rag2tm1Fwa
Tg(TcraN15,TcrbN15)L2Elre/?

involves: 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• there are almost 10-fold less CD4 T cells in the spleen
• there are about 4-fold more CD8 T cells in the spleen
• CD8 T cells proliferate when presented VSV8 peptide by antigen presenting cells
• the majority of T cells in the thymus are arrested at the double positive stage
• single positive CD4 positive T cells are absent in the thymus
• there is a reduced percentage of single positive CD8 positive T cells
• however, the TCR transgene rescues the arrestment of T cells in the double negative stage that occurs in Rag2 deficient background
• injection of the VSV8 antigen leads to rapid apoptosis and depletion of double-positive thymocytes with a 3-6 fold drop in total number of thymocytes
• CD8 positive T cells exhibit increased cytotoxicity towards cells loaded with VSV8 peptide

hematopoietic system
• there are almost 10-fold less CD4 T cells in the spleen
• there are about 4-fold more CD8 T cells in the spleen
• CD8 T cells proliferate when presented VSV8 peptide by antigen presenting cells
• the majority of T cells in the thymus are arrested at the double positive stage
• single positive CD4 positive T cells are absent in the thymus
• there is a reduced percentage of single positive CD8 positive T cells
• however, the TCR transgene rescues the arrestment of T cells in the double negative stage that occurs in Rag2 deficient background
• injection of the VSV8 antigen leads to rapid apoptosis and depletion of double-positive thymocytes with a 3-6 fold drop in total number of thymocytes
• CD8 positive T cells exhibit increased cytotoxicity towards cells loaded with VSV8 peptide


Mouse Genome Informatics
cx13
    H2b/H2d
Themistm1Gasc/Themistm1Gasc

involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• superantigen-mediated deletion of T cells expressing Vbeta5, Vbeta11, and Vbeta12 is less efficient in these mice

immune system
• superantigen-mediated deletion of T cells expressing Vbeta5, Vbeta11, and Vbeta12 is less efficient in these mice


Mouse Genome Informatics
cx14
    Apobec3Gt(XN450)Byg/Apobec3Rfv3-s
H2b/H2b

involves: A.BY * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the levels of neutralizing antibody produced to Friend virus 28 days after inoculation is over an order of magnitude lower than in littermate controls

hematopoietic system
• the levels of neutralizing antibody produced to Friend virus 28 days after inoculation is over an order of magnitude lower than in littermate controls


Mouse Genome Informatics
cx15
    H2b/H2s
Tg(TcraTcrb)1100Mjb/?

involves: A/WySn * C57BL/6 * C57BL/10Sg * Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the thymus is smaller than normal
• decreased number of CD8 T cells are found in both the thymus and in the periphery
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR

hematopoietic system
• the thymus is smaller than normal
• decreased number of CD8 T cells are found in both the thymus and in the periphery
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR

endocrine/exocrine glands
• the thymus is smaller than normal


Mouse Genome Informatics
cx16
    H2b/H2d
Tg(TcraTcrb)1100Mjb/?

involves: BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the thymus is smaller than normal
• decreased number of CD8 T cells are found in both the thymus and in the periphery
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR

hematopoietic system
• the thymus is smaller than normal
• decreased number of CD8 T cells are found in both the thymus and in the periphery
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR

endocrine/exocrine glands
• the thymus is smaller than normal


Mouse Genome Informatics
cx17
    Apobec3Gt(XN450)Byg/Apobec3Rfv3-s
H2b/H2d

involves: BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• less than 40% of mice survive viral infection when infected with 140 spleen focus forming units of Friend virus compared to 90% survival in littermate controls

immune system
• the levels of neutralizing antibody produced to Friend virus 28 days after inoculation is over an order of magnitude lower than in controls
• 16-week old mice mice infected with Friend virus have an order of magnitude more virus in their blood 8 days later than in littermate controls
• less than 40% of mice survive viral infection when infected with 140 spleen focus forming units of Friend virus compared to 90% survival in littermate controls

hematopoietic system
• the levels of neutralizing antibody produced to Friend virus 28 days after inoculation is over an order of magnitude lower than in controls


Mouse Genome Informatics
cx18
    H2b/H2d
Tg(Ins2-E3)1Dvs/0

involves: BALB/c * C57BL/6 * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• when transferred into BALB/c hosts, but not C57BL/6 hosts, pancreatic islets from H2 survive much longer than non-transgenic pancreatic islets


Mouse Genome Informatics
cx19
    H2b/H2b
Itktm1Ljb/Itktm1Ljb
Tg(TcrAND)53Hed/?

involves: C3H/HeJ * C57BL/6 * C57BL/10
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• there are almost no mature transgenic CD4 T cells in the periphery
• thymocytes take longer to undergo positive selection than wild-type thymocytes based on expression of CD69 and HSA
• expression of CD5, which is correlated with TCR signal strength, is also decreased

hematopoietic system
• there are almost no mature transgenic CD4 T cells in the periphery
• thymocytes take longer to undergo positive selection than wild-type thymocytes based on expression of CD69 and HSA
• expression of CD5, which is correlated with TCR signal strength, is also decreased


Mouse Genome Informatics
cx20
    H2b/H2k
Itktm1Ljb/Itktm1Ljb
Tg(TcrAND)53Hed/?

involves: C3H/HeJ * C57BL/6 * C57BL/10
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the development of transgenic CD4 T cells is reduced 2- to 3-fold in these mice
• thymocytes take longer to undergo positive selection than wild-type thymocytes based on expression of CD69 and HSA
• expression of CD5, which is correlated with TCR signal strength, is also decreased

hematopoietic system
• the development of transgenic CD4 T cells is reduced 2- to 3-fold in these mice
• thymocytes take longer to undergo positive selection than wild-type thymocytes based on expression of CD69 and HSA
• expression of CD5, which is correlated with TCR signal strength, is also decreased


Mouse Genome Informatics
cx21
    H2b/H2k
Tg(TcraTcrb)1100Mjb/?

involves: C57BL/6 * C57BL/10Sg * C57BR/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the thymus is smaller than normal
• decreased number of CD8 T cells are found in both the thymus and in the periphery
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR

hematopoietic system
• the thymus is smaller than normal
• decreased number of CD8 T cells are found in both the thymus and in the periphery
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR

endocrine/exocrine glands
• the thymus is smaller than normal


Mouse Genome Informatics
cx22
    H2b/H2g7
Tg(TcraR28,TcrbR28)KRNDim/0

involves: C57BL/6 * NOD * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• rheumatoid arthritis occurs with disease onset transpiring between 25 and 35 days of age
• arthritis occurrence is established by joint inspection and measure of ankle thickness, and histological confirmation in several mice

skeleton
• rheumatoid arthritis occurs with disease onset transpiring between 25 and 35 days of age
• arthritis occurrence is established by joint inspection and measure of ankle thickness, and histological confirmation in several mice

Mouse Models of Human Disease
OMIM IDRef(s)
Rheumatoid Arthritis; RA 180300 J:36815


Mouse Genome Informatics
cx23
    Airetm1.1Doi/Airetm1.1Doi
H2b/H2b

NOD.Cg-Airetm1.1Doi H2b/Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• Background Sensitivity: stomach inflammation is present regardless of the alleles found at the H2 locus

digestive/alimentary system
• Background Sensitivity: stomach inflammation is present regardless of the alleles found at the H2 locus

endocrine/exocrine glands
• Background Sensitivity: the pancreatitis associated with the Aire allele on the NOD background is absent when the H2 allele is present at homozygocity