Mouse Genome Informatics
hm1
    Ighmtm1Cgn/Ighmtm1Cgn
B6.129S2-Ighmtm1Cgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• migration of proliferated intestinal epithelial cells (IEC) toward the top of the villi and the number of proliferating IECs are augmented in mutants compared to wild-type controls
• treatment of mice with antibiotics results in deceleration of IEC migration and decreased proliferation compared to treated heterozygous controls

hematopoietic system
• population is ~2 times larger than in heterozygous controls

immune system
• population is ~2 times larger than in heterozygous controls


Mouse Genome Informatics
hm2
    Ighmtm1Cgn/Ighmtm1Cgn
B6.129S2-Ighmtm1Cgn/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• T cell numbers in lymph nodes are normal (J:73100)
• dendritic cells show normal function in mutants (J:118565)
• numbers of CD11c+ dendritic cells (DCs) are reduced in mutants
• numbers are reduced 3-fold in spleen vs wild-type (J:73100)
• there are 5- to 40-fold fewer antigen specific CD4 cells producing Il-2 in mutants compared to controls 6 months after keyhole limpet hemocyanin immunization (J:118565)
• numbers are reduced 3-fold in spleen vs wild-type
• a transitional block in early B cell development in evident in bone marrow; pre-B cells are decreased in number
• in mutants, area of T zone stromal cell network in the spleen is decreased four- to five-fold compared to wild-type
• T zone cross sectional area is decreased 2- to 3-fold
• spleens are ~50% the weight of wild-type spleens
• mice fail to respond to T cell-dependent (OVA) or T cell-independent (dextra) antigenic stimulation and do not produce serum specific antibodies to these antigens
• null mice have almost undetectable serum levels of IgG1, IgG2a, IgG2b, IgG3, IgM and IgA compared to wild-type controls or Faslpr mice
• IgE is not detectable in serum of OVA-treated mutants, but high levels are produced in treated wild-type
• IgG levels drop rapidly after birth due to loss of maternal Ig (J:119584)
• IgG is not detectable in OVA-treated mutants, but high levels are produced in treated wild-type (J:125656)
• IgG1 is not detected in serum after OVA challenge
• in mutants, Il-2 secretion is diminished from T cells primed in absence of B cells compared to controls 6 months after keyhole limpet hemocyanin immunization
• mice fail to clear a Giardia muris infection
• two weeks after Giardia infection, there are 10-fold more Giardia cysts present in the feces of mice
• mice have 10-fold more Giardia trophozoites in the small intestine three weeks after infection and a thousand-fold more 7 weeks after infection compared to controls
• mutant mice still have an active Giardia population in the gut one year after infection while wild-type mice clear Giardia after about 7 weeks
• mice are not protected from Giardia upon a secondary challenge as wild-type mice are

hematopoietic system
• numbers of CD11c+ dendritic cells (DCs) are reduced in mutants
• numbers are reduced 3-fold in spleen vs wild-type (J:73100)
• there are 5- to 40-fold fewer antigen specific CD4 cells producing Il-2 in mutants compared to controls 6 months after keyhole limpet hemocyanin immunization (J:118565)
• numbers are reduced 3-fold in spleen vs wild-type
• a transitional block in early B cell development in evident in bone marrow; pre-B cells are decreased in number
• in mutants, area of T zone stromal cell network in the spleen is decreased four- to five-fold compared to wild-type
• T zone cross sectional area is decreased 2- to 3-fold
• spleens are ~50% the weight of wild-type spleens
• null mice have almost undetectable serum levels of IgG1, IgG2a, IgG2b, IgG3, IgM and IgA compared to wild-type controls or Faslpr mice
• IgE is not detectable in serum of OVA-treated mutants, but high levels are produced in treated wild-type
• IgG levels drop rapidly after birth due to loss of maternal Ig (J:119584)
• IgG is not detectable in OVA-treated mutants, but high levels are produced in treated wild-type (J:125656)
• IgG1 is not detected in serum after OVA challenge

respiratory system
• ovalbumin-sensitized/challenged mice (OVA) are unable to generate an early phase reaction (EPR- initial phase of brochoconstriction) following OVA provocation

cardiovascular system
• mutants are protected from developing elastase-induced abdominal aortic aneurysm

homeostasis/metabolism
• mutants are protected from developing elastase-induced abdominal aortic aneurysm
• reconstitution of mutants with mouse natural antibodies from pooled sera of wild-type mice does not restore susceptibility to abdominal aortic aneurysm in mutants, however reconstitution with pooled mouse IgG to the wild-type level renders mutants susceptible to abdominal aortic aneurysm

skeleton
• significantly decreased at 10 weeks of age
• reduced trabecular bone structure in femora
• reduced number of trabeculae


Mouse Genome Informatics
hm3
    Ighmtm1Cgn/Ighmtm1Cgn
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• in bone marrow and spleen, mature (B220+) B lymphocytes are lacking
• B cell development is halted at pre-B cell stage, indicated by lack of CD25+ B-cells
• CD4+ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro
• marginal metallophilic macrophages are absent
• sinus lining cells (MAdCAM-1+) are absent
• CD4+ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro
• follicular dendritic cells are absent
• footpad swelling of antigen-sensitized mice is less than controls
• CD4+ T cells have normal primary responses suggesting lower T cell activity from immunized mice is a failure in antigen presentation
• after second infestation to ticks, mice fail to exhibit resistance (repletion) unlike similarly treated wild-type mice

hematopoietic system
• in bone marrow and spleen, mature (B220+) B lymphocytes are lacking
• B cell development is halted at pre-B cell stage, indicated by lack of CD25+ B-cells
• CD4+ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro
• marginal metallophilic macrophages are absent
• sinus lining cells (MAdCAM-1+) are absent
• CD4+ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro

skeleton


Mouse Genome Informatics
hm4
    Ighmtm1Cgn/Ighmtm1Cgn
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
N
• mucosal-associated invariant T cells (MAIT) that are not found in mice lacking all B cells are found in normal amounts in these mice (J:113083)
• no B cells are detected in the peritoneal cavity; no cells expressing IgM or IgD on their surface are detected in the peritoneal cavity
• peripheral blood and spleen lack mature B cells as shown by lack of CD45R(B220)bright cells
• mutants appear to have large pre-B cells, but not small pre-B cells, indicating arrest of differentiation at the pre-B cell stage at or close to the transition from the large to small pre-B cell (J:64298)
• in heterozygotes, normal numbers of B cells are produced, but there is loss of H-chain allelic exclusion; B cells producing H chains from both endogenous loci are detected, but such cells are absent in wild-type mice (J:70398)
• development appears to arrest differentiation of B cells at or close to the transition from the large to small pre-B cell
• homozygotes have no detectable IgM in their serum compared to ~600ug IgM/ml in wild-type serum
• upon infection with Mycoplasma pulmonis, airway lymphatic vessel remodeling is largely absent from mutants, compared to significant invasion of region by lymphatic vessels in infected wild-type mice
• bacteria are present in liver and kidney of mice after 4 weeks of M. pulmonis infection, but bacteria are absent from wild-type mouse tissue
• airway vascular and airway lymphatic vessel remodeling are impaired or absent compared to wild-type mice after M. pulmonis infection

hematopoietic system
• no B cells are detected in the peritoneal cavity; no cells expressing IgM or IgD on their surface are detected in the peritoneal cavity
• peripheral blood and spleen lack mature B cells as shown by lack of CD45R(B220)bright cells
• mutants appear to have large pre-B cells, but not small pre-B cells, indicating arrest of differentiation at the pre-B cell stage at or close to the transition from the large to small pre-B cell (J:64298)
• in heterozygotes, normal numbers of B cells are produced, but there is loss of H-chain allelic exclusion; B cells producing H chains from both endogenous loci are detected, but such cells are absent in wild-type mice (J:70398)
• development appears to arrest differentiation of B cells at or close to the transition from the large to small pre-B cell
• homozygotes have no detectable IgM in their serum compared to ~600ug IgM/ml in wild-type serum

respiratory system
N
• trachea of infected mice contain more mucin than infected wild-type tracheas (J:119344)
• after 4 weeks, mice show absence of vascular remodeling of the airways in response to Mycoplasma pulmonis infection wherease wild-type show complex growth and reorganization of the vascular beds
• although epithelial cell hyperplasia is not observed, epithelial layer is abnormally elongated


Mouse Genome Informatics
hm5
    Ighmtm1Cgn/Ighmtm1Cgn
NOD.129S2-Ighmtm1Cgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• no male or female homozygotes develop diabetes (assessed by glycosuric levels >3) by 20 weeks of age

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:37287


Mouse Genome Informatics
hm6
    Ighmtm1Cgn/Ighmtm1Cgn
NOD.129S2-Ighmtm1Cgn/DvsJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• B cells are absent in the spleen
• the proportion, but not the number, of CD 4 and CD8 T cells found in the spleen is increased due to the absence of B cells
• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD
• follicles do not develop in the spleen
• 13.6% of female mice develop diabetes by 21 weeks of age compared to control NOD mice that have an incidence rate of 95.5% at this age

hematopoietic system
• B cells are absent in the spleen
• the proportion, but not the number, of CD 4 and CD8 T cells found in the spleen is increased due to the absence of B cells
• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD
• follicles do not develop in the spleen

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:80859


Mouse Genome Informatics
hm7
    Ighmtm1Cgn/Ighmtm1Cgn
NODCaj.129S2-Ighmtm1Cgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mice display insulitis starting at 8 weeks; insulitis is milder than that observed in NOD control mice

immune system
• mice display insulitis starting at 8 weeks; insulitis is milder than that observed in NOD control mice


Mouse Genome Informatics
ht8
    Ighmtm1Cgn/Ighm+
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
• B cell development is arrested at the stage of pre-B cells

immune system
• B cell development is arrested at the stage of pre-B cells


Mouse Genome Informatics
ht9
    Ighmtm1Cgn/Ighm+
NOD.129S2-Ighmtm1Cgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• 90% of female and 45% of male heterozygotes develop diabetes (glycosuric values >3) by 20 weeks of age compared to 0% of homozygotes

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:37287


Mouse Genome Informatics
cx10
    Ighmtm1Cgn/Ighmtm1Cgn
Igkctm1Bgmn/Igkctm1Bgmn
Igltm2.1Bgmn/Igltm2.1Bgmn

involves: 129
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• IgG is not present in the sera
• IgM is not present in the sera

hematopoietic system
• IgG is not present in the sera
• IgM is not present in the sera


Mouse Genome Informatics
cx11
    Ighmtm1Cgn/Ightm3Tim
involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• B cell in mutants are reduced in the spleen, bone marrow and LNs
• preferentially promoted development to marginal zone B cell
• inefficiently drives bone marrow B lymphopoiesis and follicular B cell development

immune system
• B cell in mutants are reduced in the spleen, bone marrow and LNs
• preferentially promoted development to marginal zone B cell
• inefficiently drives bone marrow B lymphopoiesis and follicular B cell development


Mouse Genome Informatics
cx12
    Ighmtm1Cgn/Ighmtm1Cgn
Unc93b1tm1.1Kmiy/Unc93b1tm1.1Kmiy

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• unlike Unc93b1tm1.1Kmiy homozygotes, mice do not exhibit premature death (J:174308)

hematopoietic system
N
• unlike in Unc93b1tm1.1Kmiy homozygotes, spleen size is normal (J:174308)
• unlike in Unc93b1tm1.1Kmiy homozygotes, mice do not exhibit differentiation towards memory CD4+ T cells (J:174308)
• not as severe as in Unc93b1tm1.1Kmiy homozygotes


Mouse Genome Informatics
cx13
    Ighmtm1Cgn/Ighmtm1Cgn
Trex1tm1Tld/Trex1tm1Tld

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• compared with Ighmtm1Cgn homozygotes
• however, the premature death observed in Trex1tm1Tld homozygotes is rescued

immune system
• as in Trex1tm1Tld homozygotes
• as in Trex1tm1Tld homozygotes
• as in Trex1tm1Tld homozygotes
• unlike in Trex1tm1Tld homozygotes

renal/urinary system
N
• unlike Trex1tm1Tld homozygotes, mice do not exhibit glomerular lesions (J:181257)
• as in Trex1tm1Tld homozygotes
• unlike in Trex1tm1Tld homozygotes

cardiovascular system
• as in Trex1tm1Tld homozygotes
• as in Trex1tm1Tld homozygotes


Mouse Genome Informatics
cx14
    Ighmtm1Cgn/Ighmtm1Cgn
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
• development and severity of inflammatory bowel disease are similar to Tnftm2Gkl/+, wild-type B2m controls

digestive/alimentary system
• development and severity of inflammatory bowel disease are similar to Tnftm2Gkl/+, wild-type B2m controls


Mouse Genome Informatics
cx15
    Faslgld/Faslgld
Ighmtm1Cgn/Ighmtm1Cgn

involves: 129S2/SvPas * C3H/HeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• mice have high levels of IgG after birth that rise to levels similar to wild-type littermates by 90 days after birth (J:119584)


Mouse Genome Informatics
cx16
    Ighmtm1Cgn/Ighmtm1Cgn
Tg(IghMyc)22Bri/0

involves: 129S2/SvPas * C57BL * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis


Mouse Genome Informatics
cx17
    Ighmtm1Cgn/Ighmtm1Cgn
Irf2tm1Mak/Irf2tm1Mak

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• mice develop similar skin symptoms to Irf2-null mice


Mouse Genome Informatics
cx18
    Ighmtm1Cgn/Ighmtm1Cgn
Nlrp1aNeut1/Nlrp1aNeut1

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
N
• no abnormal neutrophil infiltration of the dermis (J:191055)


Mouse Genome Informatics
cx19
    Ighmtm1Cgn/Ighmtm1Cgn
Tgfb1tm1Doe/Tgfb1tm1Doe

involves: 129S2/SvPas * C57BL/6 * CF-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice survive for a median of 35 days

growth/size
• mutants display a wasting syndrome which results in death 2-5 days after the start of weight loss

immune system
• animals display decreased thymic cellularity
• animals develop inflammation similar to that displayed by Tgfb1 nulls, although this is delayed by about 2 weeks

hematopoietic system
• animals display decreased thymic cellularity

endocrine/exocrine glands
• animals display decreased thymic cellularity


Mouse Genome Informatics
cx20
    Ighmtm1Cgn/Ighm+
Tgfb1tm1Doe/Tgfb1tm1Doe

involves: 129S2/SvPas * C57BL/6 * CF-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• splenocytes of Day 12-19 mutants are hyperresponsive to LPS stimulation in culture compared to Igh-6 heterozygous splenocytes

immune system
• animals display decreased thymic cellularity

hematopoietic system
• animals display decreased thymic cellularity

endocrine/exocrine glands
• animals display decreased thymic cellularity


Mouse Genome Informatics
cx21
    Ighmtm1Cgn/Ighmtm1Cgn
Tg(Ins2-Cxcl13)1Cys/0

involves: 129S2/SvPas * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• very few infiltrates of pancreatic islets are observed
• infiltrates are B cell dominated, but majority also contain T cells; there is a 10-fold increase in T cell-containing infiltrates in transgenic B cell-deficient mice
• some infiltrates become medium or large-sized and are composed mainly of CD4+ T cells


Mouse Genome Informatics
cx22
    Faslpr/Faslpr
Ighmtm1Cgn/Ighmtm1Cgn

involves: 129S2/SvPas * C57BL/6 * MRL/Mp
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• number of Ig-positive B cells in spleen are 10- to 20-fold lower than in wild-type or Faslpr mice
• cell outgrowth in lymphadenopathy is dominated by Tcrb/B220+ cells
• a transitional block in early B cell development in evident in bone marrow; pre-B cells are decreased in number
• at 8-10 weeks of age, mice develop significant lymphadenopathy
• mice fail to respond to T cell-dependent (OVA) or T cell-independent (dextra) antigenic stimulation and do not produce serum specific antibodies to these antigens
• levels of IgG2a and IgA are elevated compared to wild-type mice; significant levels (up to 10-fold) of serum antibodies have the gamma light chain isotype compared to control
• levels are much lower than in controls, comparable to Igh-6 single nulls
• mice have high titers of chromatin antibodies compared to controls and titer increased with age; anti-cardiolipin antibodies are increased in serum in 40% of double mutants

hematopoietic system
• number of Ig-positive B cells in spleen are 10- to 20-fold lower than in wild-type or Faslpr mice
• cell outgrowth in lymphadenopathy is dominated by Tcrb/B220+ cells
• a transitional block in early B cell development in evident in bone marrow; pre-B cells are decreased in number
• levels of IgG2a and IgA are elevated compared to wild-type mice; significant levels (up to 10-fold) of serum antibodies have the gamma light chain isotype compared to control
• levels are much lower than in controls, comparable to Igh-6 single nulls

homeostasis/metabolism
• mice show significant proteinuria

renal/urinary system
• mice show significant proteinuria


Mouse Genome Informatics
cx23
    Ighmtm1Cgn/Ighmtm1Cgn
Tg(TcraR28,TcrbR28)KRNDim/0

involves: 129S2/SvPas * 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
N
• arthritis does not occur in these mice (J:36815)

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Rheumatoid Arthritis; RA 180300 J:36815


Mouse Genome Informatics
cx24
    H2-Ab1tm1Gru/H2-Ab1tm1Gru
Ighmtm1Cgn/Ighmtm1Cgn
Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

NOD.Cg-Ighmtm1Cgn H2-Ab1tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• magnitude of cardiac enlargement is similar to NOD transgenic H2-Ab1-null, Igh-6-sufficient mice
• appearance of heart block is not significantly different from NOD transgenic H2-Ab1-null, Igh-6-sufficient mice
• at 22 weeks, mice show mononuclear cell infiltrates in heart walls

immune system
• at 22 weeks, mice show mononuclear cell infiltrates in heart walls


Mouse Genome Informatics
cx25
    Ighmtm1Cgn/Ighmtm1Cgn
Tg(Igh-6/Igh-V125)2Jwt/0
Tg(Igk-C/Igk-V125)1Jwt/0

NOD.Cg-Ighmtm1Cgn Tg(Igh-6/Igh-V125)2Jwt Tg(Igk-C/Igk-V125)1Jwt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• by 40 weeks, pancreata of transgenic mice show extensive infiltrates; at 6 weeks, in the early prediabetic period, the incidence of infiltration is 40-50%

immune system
• by 40 weeks, pancreata of transgenic mice show extensive infiltrates; at 6 weeks, in the early prediabetic period, the incidence of infiltration is 40-50%


Mouse Genome Informatics
cx26
    Ighmtm1Cgn/Ighm+
Tg(Igh-6/Igh-V125)2Jwt/0
Tg(Igk-C/Igk-V125)1Jwt/0

NOD.Cg-Ighmtm1Cgn Tg(Igh-6/Igh-V125)2Jwt Tg(Igk-C/Igk-V125)1Jwt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• the percentage of islets infiltrated is slightly increased in Igh-6-heterozygous transgenic mice

immune system
• the percentage of islets infiltrated is slightly increased in Igh-6-heterozygous transgenic mice
• transgenic females heterozygous for Igh-6 develop diabetes (2 consecutive blood glucose measurements >200 mg/dl) at a slightly earlier time (12 weeks) than homozygous transgenic females but the incidence is the same by 17 weeks

homeostasis/metabolism


Mouse Genome Informatics
cx27
    Ighmtm1Cgn/Ighmtm1Cgn
Tg(Igh-6/Igh-V281)3Jwt/0

NOD.Cg-Ighmtm1Cgn Tg(Igh-6/Igh-V281)3Jwt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• by 40 weeks, pancreata of transgenic mice show extensive infiltrates; at 6 weeks, in the early prediabetic period, the incidence of infiltration is 40-50% slightly less than mice carrying the V281 transgene; the percentage of islets infiltrated is slightly greater in transgenic mice heterozygous for Igh-6

immune system
• by 40 weeks, pancreata of transgenic mice show extensive infiltrates; at 6 weeks, in the early prediabetic period, the incidence of infiltration is 40-50% slightly less than mice carrying the V281 transgene; the percentage of islets infiltrated is slightly greater in transgenic mice heterozygous for Igh-6


Mouse Genome Informatics
cx28
    Ighmtm1Cgn/Ighm+
Tg(Igh-6/Igh-V281)3Jwt/0

NOD.Cg-Ighmtm1Cgn Tg(Igh-6/Igh-V281)3Jwt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• the percentage of islets infiltrated is slightly greater in transgenic mice heterozygous for Igh-6

immune system
• the percentage of islets infiltrated is slightly greater in transgenic mice heterozygous for Igh-6

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:91865


Mouse Genome Informatics
cx29
    Ighmtm1Cgn/Ighmtm1Cgn
Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg

NOD.Cg-Ighmtm1Cgn Tg(IghelMD4)4Ccg/DvsJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice have low levels of insulitis starting at 12 weeks of age with a mean disease score of 1.62 compared to non-transgenic NOD mice that have a mean score of 3.01 at this age
• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice
• the number but not the proportion of B cells found in the spleen is twice that of non-transgenic NOD mice
• all of the B cells express the transgenic IgM B cell receptor specific for hen egg lysozyme
• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD
• purified B cells fail to stimulate T cells from non-transgenic NOD mice when cultured together in the presence of the diabetes autoantigen GAD
• 16.7% of female mice develop diabetes by 21 weeks of age compared to control NOD mice that have an incidence rate of 95.5% at this age
• mice with lymphosarcomas were not included in the analysis

tumorigenesis
• lymphosarcomas are present in the majority of mice with development starting at 20 weeks of age

hematopoietic system
• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice
• the number but not the proportion of B cells found in the spleen is twice that of non-transgenic NOD mice
• all of the B cells express the transgenic IgM B cell receptor specific for hen egg lysozyme
• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD
• purified B cells fail to stimulate T cells from non-transgenic NOD mice when cultured together in the presence of the diabetes autoantigen GAD

endocrine/exocrine glands
• mice have low levels of insulitis starting at 12 weeks of age with a mean disease score of 1.62 compared to non-transgenic NOD mice that have a mean score of 3.01 at this age

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:80859


Mouse Genome Informatics
cx30
    Ighmtm1Cgn/Ighmtm1Cgn
Tg(Igh-VB1-8/Igh-6m)1Mjsk/?

NODCaj.Cg-Ighmtm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• female Igh-6-deficient transgenic mice show a 7-fold increase in the incidence of (blood glucose >250 mg/dl) diabetes compared with nontransgenic littermates

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:93190