Mouse Genome Informatics
hm1
    B2mtm1Jae/B2mtm1Jae
B6.129S2-B2mtm1Jae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• spleen and lymph node cells produce an average of 5-fold higher levels of IL-3
• spleen and lymph node cells produce IFN gamma at comparable levels to wild-type at 8 weeks after parasite infection
• no IL-4 was detected at any time
• spleen and lymph node cells produce an average of 3.7-fold higher levels of LT-TNF
• lesions after infection progress similarly to those in wild-type up to 7 weeks post-infection, then decrease slightly in size and remain a constant size over a 23-week period

nervous system
• area of the ipsilateral projection is increased compared to controls


Mouse Genome Informatics
hm2
    B2mtm1Jae/B2mtm1Jae
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• abnormal deposits of ferric iron in liver and increased total hepatic iron levels (1583 ug/g dry tissue vs. 468 ug/g in wildtype)
• occasionally saw deposits of ferric iron in myocytes, in the branchial wall and lumen of the lung, in the pancreas, and in 5 week old marginal zone of the spleen

hematopoietic system
• in the spleen and thymus

immune system
• in the spleen and thymus


Mouse Genome Informatics
hm3
    B2mtm1Jae/B2mtm1Jae
involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• decreased proportion of CD8+ alpha-beta+ T cells (J:744)
• 100-150-fold reduction in T-cell antigen receptor alpha-beta+ CD4-CD8+ T cells in adult thymus and spleen, however levels of gamma-delta T cells is normal (J:80910)
• frequency of gamma-delta+ T cells was considerably higher in the thymus (11% vs. 6.5% of CD4-CD8- thymocytes), however development and functional competence of gamma-delta+ T cells was normal
• increased frequency of gamma-delta+ T cells in the intestinal epithelium
• spleen cells did not contain cytotoxic T lymphocyte precursors
• spleen cells fail to generate allo-specific cytotoxic T lympocyte response when stimulated with BALB/c (H-2d) spleen cells

immune system
• decreased proportion of CD8+ alpha-beta+ T cells (J:744)
• 100-150-fold reduction in T-cell antigen receptor alpha-beta+ CD4-CD8+ T cells in adult thymus and spleen, however levels of gamma-delta T cells is normal (J:80910)
• frequency of gamma-delta+ T cells was considerably higher in the thymus (11% vs. 6.5% of CD4-CD8- thymocytes), however development and functional competence of gamma-delta+ T cells was normal
• increased frequency of gamma-delta+ T cells in the intestinal epithelium
• spleen cells did not contain cytotoxic T lymphocyte precursors
• spleen cells fail to generate allo-specific cytotoxic T lympocyte response when stimulated with BALB/c (H-2d) spleen cells


Mouse Genome Informatics
cn4
    B2mtm1Jae/B2mtm1Jae
Tg(B2m)1Rms/0
Tg(INS-cre)2Rms/0

involves: 129S2/SvPas * NOD
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• resistance to development of diabetes and hyperglycemia

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:83635


Mouse Genome Informatics
cx5
    B2mtm1Jae/B2mtm1Jae
Tap1tm1Hpl/Tap1tm1Hpl

B6.129-B2mtm1Jae Tap1tm1Hpl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 52% of P13 mice and 57% of adult mice have enlarged lateral ventricles
• area of the ipsilateral projection is increased compared to controls
• in some cases, multiple ectopic clusters of inputs are present in the medial areas of the LGN
• retinogeniculate axons, glomeruli and bouton appear normal
• increase in size of excitatory presynaptic boutons
• mice exhibit significantly fewer perforations at hippocampal synapses that wild-type
• presynaptic nerve terminals contain 10% more synaptic vesicles than wild-type
• LTP in response to tetanus is enhanced by approximately 227% as compared to wild type
• 40% increase in frequency in hippocampal neurons
• 100% increase in frequency in layer 4 cortical neurons
• median amplitude is similar to wild-type in hippocampal and layer 4 neurons
• treatment with the neural activity blocker, Tetrodotoxin (TTX), does not increase mEPSC in mutant hippocampal cultures in contrast to increases in both amplitude and frequency observed in wild-type
• 900 pulses at 1 Hz enhances baseline LTD, but LTD is unchanged in wild-type
• 900 pulses at 0.5 Hz does not induce significant LTD in contrast to wild-type response


Mouse Genome Informatics
cx6
    B2mtm1Jae/B2mtm1Jae
Themistm1Lov/Themistm1Lov

involves: 129
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• CD3hi CD8 single-positive thymocytes are present in these mice
• these thymocytes are TCRhiCD69+ which indicates that they received positively selecting signals by interaction with self peptide-MHC class II complexes but are subsequently 'redirected' to the CD8 lineage

hematopoietic system
• CD3hi CD8 single-positive thymocytes are present in these mice
• these thymocytes are TCRhiCD69+ which indicates that they received positively selecting signals by interaction with self peptide-MHC class II complexes but are subsequently 'redirected' to the CD8 lineage


Mouse Genome Informatics
cx7
    B2mtm1Jae/B2mtm1Jae
Foxp3sfOtcspf/Y

involves: 129/Rl * 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size

immune system
• plasma cell hyperplasia within the spleen and lymph nodes (J:20865)
• greater percentage of CD45RBdullCD4+ T cells than in homozygous B2m mice (J:20865)
• increased amounts of IL-4, IL-6, and IL-10 and decreased amounts of IL-2 in Con A stimulated day 16 splenocytes (J:20865)
• decreased amount of TNF-alpha in Con A stimulated day 16 splenocytes (J:20865)
(J:20865)
• complete disruption of normal architecture, with abundant lymphoblasts and reticular cell hyperplasia (J:20865)
• exfoliative dermatitis (J:20865)

hematopoietic system
(J:20865)
• plasma cell hyperplasia within the spleen and lymph nodes (J:20865)
• greater percentage of CD45RBdullCD4+ T cells than in homozygous B2m mice (J:20865)
(J:20865)

homeostasis/metabolism
• increased amounts of IL-4, IL-6, and IL-10 and decreased amounts of IL-2 in Con A stimulated day 16 splenocytes (J:20865)
• decreased amount of TNF-alpha in Con A stimulated day 16 splenocytes (J:20865)

integument
• exfoliative dermatitis (J:20865)


Mouse Genome Informatics
cx8
    B2mtm1Jae/B2mtm1Jae
Cd4tm1.1Yzo/Cd4tm1.1Yzo

involves: 129P2/OlaHsd * 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the peripheral CD4+CD8+ double positive T cells observed in Cd4tm1.1Yzo homozygotes are absent in these mice demonstrating Class I-dependence of this cell population

hematopoietic system
• the peripheral CD4+CD8+ double positive T cells observed in Cd4tm1.1Yzo homozygotes are absent in these mice demonstrating Class I-dependence of this cell population


Mouse Genome Informatics
cx9
    B2mtm1Jae/B2mtm1Jae
Cd4tm3.2Litt/Cd4tm3.2Litt

involves: 129P2/OlaHsd * 129S2/SvPas * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice
• the frequency of TCRbetahi thymocyte is decreased 10-fold compared to in wild-type mice
• mice exhibit peripheral TCRbeta<+> T cells that do not express CD4 or CD8 unlike in wild-type mice
• mice exhibit a reduction in mature thymocyte output compared with wild-type mice
• however, the expression of CD4 in post-selection thymocytes is normal
• thymocytes exhibit lymphopenia-induced homeostatic proliferation in the periphery unlike in wild-type mice

hematopoietic system
• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice
• mice exhibit a reduction in mature thymocyte output compared with wild-type mice
• the frequency of TCRbetahi thymocyte is decreased 10-fold compared to in wild-type mice
• mice exhibit peripheral TCRbeta<+> T cells that do not express CD4 or CD8 unlike in wild-type mice
• however, the expression of CD4 in post-selection thymocytes is normal
• thymocytes exhibit lymphopenia-induced homeostatic proliferation in the periphery unlike in wild-type mice


Mouse Genome Informatics
cx10
    B2mtm1Jae/B2mtm1Jae
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice display delayed development and attenuation of inflammatory bowel disease

digestive/alimentary system
• mice display delayed development and attenuation of inflammatory bowel disease


Mouse Genome Informatics
cx11
    B2mtm1Jae/B2mtm1Jae
Cd4tm1Jrp/Cd4tm1Jrp

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• an increase in CD8+ T cells similar to that seen in single Cd4tm1Jrp mutants

immune system
• an increase in CD8+ T cells similar to that seen in single Cd4tm1Jrp mutants


Mouse Genome Informatics
cx12
    B2mtm1Jae/B2mtm1Jae
Zbtb7btm1Litt/Zbtb7btm1.2Litt

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• single-positive CD8+ cells are found among mature thymocytes compared to mice null for just the B2m locus that have no mature CD8+ thymocytes
• an unusual double-positive thymocyte population exists that has surface markers of mature single positive thymocytes (HSAlo-neg TCRbetahi) and may represent single-positive CD4+ thymoyctes that are redirected to a CD8+ T cell lineage

hematopoietic system
• single-positive CD8+ cells are found among mature thymocytes compared to mice null for just the B2m locus that have no mature CD8+ thymocytes
• an unusual double-positive thymocyte population exists that has surface markers of mature single positive thymocytes (HSAlo-neg TCRbetahi) and may represent single-positive CD4+ thymoyctes that are redirected to a CD8+ T cell lineage


Mouse Genome Informatics
cx13
    B2mtm1Jae/B2mtm1Jae
Tg(H2-K-Cd86)27All/0

involves: 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• no B cells are detected in blood of B2m-deficient transgenic mice

immune system
• no B cells are detected in blood of B2m-deficient transgenic mice


Mouse Genome Informatics
cx14
    B2mtm1Jae/B2mtm1Jae
Tg(LckNotch1)9Erob/?

involves: 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice have 2-fold more mature single-positive CD8 thymocytes than wild-type mice and over a 1000-fold more than fold in B2m homozygote controls
• in the periphery, CD8+ T cells make up 2% of the lymph node population compared to less than 0.1% for B2m homozygote controls
• lymph node cellularity is 25% that of controls, with a normal ratio between CD4+ and CD8+ T cells

hematopoietic system
• mice have 2-fold more mature single-positive CD8 thymocytes than wild-type mice and over a 1000-fold more than fold in B2m homozygote controls
• in the periphery, CD8+ T cells make up 2% of the lymph node population compared to less than 0.1% for B2m homozygote controls


Mouse Genome Informatics
cx15
    B2mtm1Jae/B2mtm1Jae
Toxtm1.1Kay/Toxtm1.1Kay

involves: 129S6/SvEvTac * 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• about twice as much CD8+ T cells are found in the thymus of double knockouts compared to mice homozygote for just the B2mtm1Jae allele
• about 5-fold more CD8+ T cells are found in the spleen of double knockouts compared to mice homozygote for just the B2mtm1Jae allele
• numbers of CD8+ T cells in both the thymus and spleen are still well below normal numbers indicating the vast majority of CD8+ T cells are Class I-dependent

hematopoietic system
• about twice as much CD8+ T cells are found in the thymus of double knockouts compared to mice homozygote for just the B2mtm1Jae allele
• about 5-fold more CD8+ T cells are found in the spleen of double knockouts compared to mice homozygote for just the B2mtm1Jae allele
• numbers of CD8+ T cells in both the thymus and spleen are still well below normal numbers indicating the vast majority of CD8+ T cells are Class I-dependent