Mouse Genome Informatics
hm1
    Btkxid/Btkxid
B6.CBA-Btkxid
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• homozygous female mice exhibit a 2-3 fold decrease in CD23+ AA4+ bone marrow B cells (T2, T3), numbers of CD23- AA4+ cells are consistent with control (J:145687)
• CD23+ AA4+ splenic B cell numbers are similar to control (J:145687)

hematopoietic system
• homozygous female mice exhibit a 2-3 fold decrease in CD23+ AA4+ bone marrow B cells (T2, T3), numbers of CD23- AA4+ cells are consistent with control (J:145687)
• CD23+ AA4+ splenic B cell numbers are similar to control (J:145687)


Mouse Genome Informatics
hm2
    Btkxid/Btkxid
CBA/CaHN-Btkxid/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• dextran sulfate sodium-induced colitis results in significant weight loss in wild-type mice by day 10 of DSS treatment while mutants do not exhibit any weight loss at that time (J:92639)
• decrease in IgDhi IgMlo mature follicular B cells (J:69477)
• total leukocyte numbers are not significantly altered compared to wild-type, but significantly reduced peripheral PMN frequency in blood is observed in mutants (J:92639)
• number of monocytic and granulocytic-lineage cells is significantly reduced in mutant bone marrow (J:92639)
• frequency of monocytic/granulocytic precursors (myeloid CFUs) is significantly reduced compared to wild-type bone marrow (J:92639)
• mutant polymorphonuclear leukocytes (PMNs) show poorer induction of reactive oxygen intermediates (ROIs) upon LPS stimulation compared to wild-type; NO production is significantly less in mutant PMNs (J:92639)
• phagocytic ability of PMNs is somewhat lower, but not significantly, compared to wild-type (J:92639)
• macrophages (adherent peritoneal exudates cells, PECs) stimulated with LPS show a reduced induction of ROIs than wild-type macrophages at all LPS concentrations (J:92639)
• mice show slower induction of experimental autoimmune encephalomyelitis (EAE) and milder clinical disease than wild-type mice (J:92639)
• peak footpad swelling in response to carrageenan injection is reduced compared to wild-type mice (J:92639)
• in Salmonella typhimurium-infected mice (J:128518)

hematopoietic system
• decrease in IgDhi IgMlo mature follicular B cells (J:69477)
• total leukocyte numbers are not significantly altered compared to wild-type, but significantly reduced peripheral PMN frequency in blood is observed in mutants (J:92639)
• number of monocytic and granulocytic-lineage cells is significantly reduced in mutant bone marrow (J:92639)
• frequency of monocytic/granulocytic precursors (myeloid CFUs) is significantly reduced compared to wild-type bone marrow (J:92639)
• mutant polymorphonuclear leukocytes (PMNs) show poorer induction of reactive oxygen intermediates (ROIs) upon LPS stimulation compared to wild-type; NO production is significantly less in mutant PMNs (J:92639)
• phagocytic ability of PMNs is somewhat lower, but not significantly, compared to wild-type (J:92639)
• macrophages (adherent peritoneal exudates cells, PECs) stimulated with LPS show a reduced induction of ROIs than wild-type macrophages at all LPS concentrations (J:92639)

digestive/alimentary system
• dextran sulfate sodium-induced colitis results in significant weight loss in wild-type mice by day 10 of DSS treatment while mutants do not exhibit any weight loss at that time (J:92639)

mortality/aging
• in Salmonella typhimurium-infected mice (J:128518)


Mouse Genome Informatics
hm3
    Btkxid/Btkxid
CBA/HN-Btkxid
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls (J:81429)
• Background Sensitivity: numbers (22%) are less than female mutants on CBA/HN * DBA/2N background (40%) (J:81429)
• incidence of B lymphocytes is slightly lower, but absolute population is not, compared to controls (J:81429)
• incidence of small lymphocytes is slightly lower, but absolute population is not, compared to controls (J:7981)
• cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells (J:81429)
• Background Sensitivity: proliferative response in B cells from females is drastically lower than in cells from female mutants on CBA/HN * DBA/2N background (J:81429)
• incidence of pre-B cells is slightly reduced, but absolute population is comparable to controls (J:7981)
• number of nucleated spleen cells (~60 x 106/spleen) is significantly lower than in controls (~120 x 106/spleen) (J:81429)
• Background Sensitivity: females have significantly less than females on the CBA/HN * DBA/2N background which have (~90 x 106/spleen) (J:81429)
• mice do not develop autoantibodies (anti-dsDNA or any IgG antinuclear autoantibodies) (J:125114)

hematopoietic system
• spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls (J:81429)
• Background Sensitivity: numbers (22%) are less than female mutants on CBA/HN * DBA/2N background (40%) (J:81429)
• incidence of B lymphocytes is slightly lower, but absolute population is not, compared to controls (J:81429)
• incidence of small lymphocytes is slightly lower, but absolute population is not, compared to controls (J:7981)
• cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells (J:81429)
• Background Sensitivity: proliferative response in B cells from females is drastically lower than in cells from female mutants on CBA/HN * DBA/2N background (J:81429)
• incidence of pre-B cells is slightly reduced, but absolute population is comparable to controls (J:7981)
• number of nucleated cells is higher in mutants than in controls (J:7981)
• number of nucleated spleen cells (~60 x 106/spleen) is significantly lower than in controls (~120 x 106/spleen) (J:81429)
• Background Sensitivity: females have significantly less than females on the CBA/HN * DBA/2N background which have (~90 x 106/spleen) (J:81429)

Mouse Models of Human Disease
OMIM IDRef(s)
Agammaglobulinemia, X-Linked; XLA 300755 J:81429


Mouse Genome Informatics
hm4
    Btkxid/Btkxid
involves: C57BL/6 * CBA
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 (i.e. MAIT cells are not dependent on B1 B cells) (J:113083)


Mouse Genome Informatics
hm5
    Btkxid/Btkxid
involves: CBA/HN * DBA/2N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• spleens from females have ~40% immunoglobulin-bearing cells compared to ~50% in controls (J:81429)
• Background Sensitivity: numbers are greater in female mutants on CBA * C57BL/6 background (40%) than females on CBA/HN background (22%) (J:81429)
• number of nucleated spleen cells (~90 x 106/spleen) is significantly lower than in controls (~120 x 106/spleen) (J:81429)
• Background Sensitivity: females on the CBA * DBA/2J (~90 x 106/spleen) have significantly more nucleated spleen cells CBA/HN females (~60 x 106/spleen) (J:81429)
• spleen cells from unsensitized females cause 3-fold higher chromium release from H-2b antibody treated EL-4 tumor cells than splenocytes from males (J:81429)
• B cells show response to LPS and poly I:C similar to wild-type cells (J:81429)
• Background Sensitivity: proliferative response in B cells from females is much higher than in cells from female mutants on CBA/HN background (J:81429)

immune system
• spleens from females have ~40% immunoglobulin-bearing cells compared to ~50% in controls (J:81429)
• Background Sensitivity: numbers are greater in female mutants on CBA * C57BL/6 background (40%) than females on CBA/HN background (22%) (J:81429)
• number of nucleated spleen cells (~90 x 106/spleen) is significantly lower than in controls (~120 x 106/spleen) (J:81429)
• Background Sensitivity: females on the CBA * DBA/2J (~90 x 106/spleen) have significantly more nucleated spleen cells CBA/HN females (~60 x 106/spleen) (J:81429)
• spleen cells from unsensitized females cause 3-fold higher chromium release from H-2b antibody treated EL-4 tumor cells than splenocytes from males (J:81429)
• B cells show response to LPS and poly I:C similar to wild-type cells (J:81429)
• Background Sensitivity: proliferative response in B cells from females is much higher than in cells from female mutants on CBA/HN background (J:81429)

Mouse Models of Human Disease
OMIM IDRef(s)
Agammaglobulinemia, X-Linked; XLA 300755 J:81429


Mouse Genome Informatics
cx6
    Btkxid/Btkxid
Ikzf3tm1Kge/Ikzf3tm1Kge

involves: 129S4/SvJae * CBA/CaHN
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• decrease in IgDhi IgMlo mature follicular B cells, similar to that seen in single homozygous Btk mutant mice (J:69477)
• however, normal numbers of marginal zone B cells are observed (J:69477)

immune system
• decrease in IgDhi IgMlo mature follicular B cells, similar to that seen in single homozygous Btk mutant mice (J:69477)
• however, normal numbers of marginal zone B cells are observed (J:69477)


Mouse Genome Informatics
cx7
    Btkxid/Y
Ikzf3tm1Kge/Ikzf3tm1Kge

involves: 129S4/SvJae * CBA/CaHN
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• decrease in IgDhi IgMlo mature follicular B cells, similar to that seen in single homozygous Btk mutant mice (J:69477)
• however, normal numbers of marginal zone B cells are observed (J:69477)

immune system
• decrease in IgDhi IgMlo mature follicular B cells, similar to that seen in single homozygous Btk mutant mice (J:69477)
• however, normal numbers of marginal zone B cells are observed (J:69477)


Mouse Genome Informatics
cx8
    Btkxid/?
Tg(IGH-Btk)1Witt/0

involves: BALB/c * C3H * C57BL/6 * CBA/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the percentage of peritoneal B220+CD5+ cells is decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene
• however, the frequency and number of splenic B cells are similar to wild-type controls
• less sensitive to anti-IgM induced proliferation compared to wild-type controls
• basal serum IgG3 levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene
• serum levels of IgM following TNP-Ficoll treatment are reduced compared to wild-type controls
• basal serum IgM levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene

hematopoietic system
• the percentage of peritoneal B220+CD5+ cells is decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene
• however, the frequency and number of splenic B cells are similar to wild-type controls
• less sensitive to anti-IgM induced proliferation compared to wild-type controls
• basal serum IgG3 levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene
• serum levels of IgM following TNP-Ficoll treatment are reduced compared to wild-type controls
• basal serum IgM levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene


Mouse Genome Informatics
cx9
    Btkxid/?
Tg(IGH-Btk)1Witt/Tg(IGH-Btk)1Witt

involves: BALB/c * C3H * C57BL/6 * CBA/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• in most mice the percentage of peritoneal B220+CD5+ cells is decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene
• however, some mice had frequencies of B1 cells near the normal range
• the frequency and number of splenic B cells are similar to wild-type controls
• less sensitive to anti-IgM induced proliferation compared to wild-type controls but more responsive than mutant mice hemizygous for the transgene
• basal serum IgG3 levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene
• serum levels of IgM following TNP-Ficoll treatment are reduced compared to wild-type controls
• basal serum IgM levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene

hematopoietic system
• in most mice the percentage of peritoneal B220+CD5+ cells is decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene
• however, some mice had frequencies of B1 cells near the normal range
• the frequency and number of splenic B cells are similar to wild-type controls
• less sensitive to anti-IgM induced proliferation compared to wild-type controls but more responsive than mutant mice hemizygous for the transgene
• basal serum IgG3 levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene
• serum levels of IgM following TNP-Ficoll treatment are reduced compared to wild-type controls
• basal serum IgM levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene


Mouse Genome Informatics
cx10
    Btkxid/?
Ptpn6me/Ptpn6me

involves: C57BL/6J * CBA/N * NFS
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: life span about 8 weeks whereas on a C57BL/6 background survival is about 3 weeks

growth/size
• weigh about 66% of control weight

limbs/digits/tail
• autoamputation of 2-3 extremities by 8 weeks of age

integument
• cutaneous granulomatous lesions at 8 weeks

immune system
• lack of stimulatory effect of ConA
• increased secretion by splenocytes in culture
• serum levels considerably lower than Ptpn6me/me controls
• very slightly elevated relative to controls

cellular
• lack of stimulatory effect of ConA

hematopoietic system
• lack of stimulatory effect of ConA
• increased secretion by splenocytes in culture
• serum levels considerably lower than Ptpn6me/me controls


Mouse Genome Informatics
ot11
    Btkxid/Y
CBA/HN-Btkxid
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls (J:81429)
• cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells (J:81429)
• number of nucleated spleen cells (~60 x 106/spleen) is significantly lower than in controls (~120 x 106/spleen) (J:81429)

hematopoietic system
• spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls (J:81429)
• cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells (J:81429)
• number of nucleated spleen cells (~60 x 106/spleen) is significantly lower than in controls (~120 x 106/spleen) (J:81429)

Mouse Models of Human Disease
OMIM IDRef(s)
Agammaglobulinemia, X-Linked; XLA 300755 J:81429


Mouse Genome Informatics
ot12
    Btkxid/Y
involves: CBA/HN * DBA/2N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls (J:81429)
• cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells (J:81429)
• proliferative response occurs slightly later and is much lower in males than in females (J:81429)
• number of nucleated spleen cells (~50 x 106/spleen) is significantly lower than in controls (~120 x 106/spleen) (J:81429)

immune system
• spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls (J:81429)
• cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells (J:81429)
• proliferative response occurs slightly later and is much lower in males than in females (J:81429)
• number of nucleated spleen cells (~50 x 106/spleen) is significantly lower than in controls (~120 x 106/spleen) (J:81429)

Mouse Models of Human Disease
OMIM IDRef(s)
Agammaglobulinemia, X-Linked; XLA 300755 J:81429


Mouse Genome Informatics
ot13
    Btkxid/?
involves: BALB/c * CBA/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the frequency and number of B cells are reduced in the spleen
• drastic reduction in the percentage of CD5+B220+ cells in the peritoneum
• no increase in proliferation is seen after BCR cross-linking
• serum levels of IgM following TNP-Ficoll treatment are reduced compared to wild-type controls
• basal serum IgM levels are decreased compared to wild-type controls

hematopoietic system
• the frequency and number of B cells are reduced in the spleen
• drastic reduction in the percentage of CD5+B220+ cells in the peritoneum
• no increase in proliferation is seen after BCR cross-linking
• serum levels of IgM following TNP-Ficoll treatment are reduced compared to wild-type controls
• basal serum IgM levels are decreased compared to wild-type controls