Phenotypes associated with this allele

• Allele Symbol: Btk^xid
• Allele Name: X linked immune deficiency
• Allele ID: MGI:1856317
• Summary: 13 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Btk^xid/Btk^xid	B6.CBA-Btk^xid	MGI:3836899
hm2	Btk^xid/Btk^xid	CBA/CaHN-Btk^xid/J	MGI:3687743
hm3	Btk^xid/Btk^xid	CBA/HN-Btk^xid	MGI:3687754
hm4	Btk^xid/Btk^xid	involves: C57BL/6 * CBA	MGI:3814825
hm5	Btk^xid/Btk^xid	involves: CBA/HN * DBA/2N	MGI:3687751
cx6	Btk^xid/Btk^xid Ikzf3^tm1Kge/Ikzf3^tm1Kge	involves: 129S4/SvJae * CBA/CaHN	MGI:4453853
cx7	Btk^xid/Y Ikzf3^tm1Kge/Ikzf3^tm1Kge	involves: 129S4/SvJae * CBA/CaHN	MGI:4453854
cx8	Btk^xid/? Tg(IGH-Btk)1Witt/0	involves: BALB/c * C3H * C57BL/6 * CBA/N	MGI:3836568
cx9	Btk^xid/? Tg(IGH-Btk)1Witt/Tg(IGH-Btk)1Witt	involves: BALB/c * C3H * C57BL/6 * CBA/N	MGI:3836569
cx10	Btk^xid/? Ptpn6^me/Ptpn6^me	involves: C57BL/6J * CBA/N * NFS	MGI:5314647
ot11	Btk^xid/Y	CBA/HN-Btk^xid	MGI:3687750
ot12	Btk^xid/Y	involves: CBA/HN * DBA/2N	MGI:3687752
ot13	Btk^xid/?	involves: BALB/c * CBA/N	MGI:3836566

Genotype
MGI:3836899

hm1

• Allelic Composition: Btk^xid/Btk^xid
• Genetic Background: B6.CBA-Btk^xid

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

immune system

decreased transitional stage B cell number ( J:145687 )

♀ • 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

♀ • CD23+ AA4+ splenic B cell numbers are similar to control

hematopoietic system

decreased transitional stage B cell number ( J:145687 )

♀ • 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

♀ • CD23+ AA4+ splenic B cell numbers are similar to control

Genotype
MGI:3687743

hm2

• Allelic Composition: Btk^xid/Btk^xid
• Genetic Background: CBA/CaHN-Btk^xid/J

immune system

increased susceptibility to induced colitis ( J:92639 )

♀ • 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

impaired myelopoiesis ( J:92639 )

♀ • number of monocytic and granulocytic-lineage cells is significantly reduced in mutant bone marrow

♀ • frequency of monocytic/granulocytic precursors (myeloid CFUs) is significantly reduced compared to wild-type bone marrow

decreased neutrophil cell number ( J:92639 )

♀ • total leukocyte numbers are not significantly altered compared to wild-type, but significantly reduced peripheral PMN frequency in blood is observed in mutants

decreased follicular B cell number ( J:69477 )

♀ • decrease in IgD^hi IgM^lo mature follicular B cells

abnormal neutrophil physiology ( 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

impaired neutrophil phagocytosis ( J:92639 )

♀ • phagocytic ability of PMNs is somewhat lower, but not significantly, compared to wild-type

abnormal macrophage physiology ( 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

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:92639 )

♀ • mice show slower induction of experimental autoimmune encephalomyelitis (EAE) and milder clinical disease than wild-type mice

decreased acute inflammation ( J:92639 )

♀ • peak footpad swelling in response to carrageenan injection is reduced compared to wild-type mice

increased susceptibility to bacterial infection induced morbidity/mortality ( J:128518 )

♀ • in Salmonella typhimurium-infected mice

hematopoietic system

impaired myelopoiesis ( J:92639 )

♀ • number of monocytic and granulocytic-lineage cells is significantly reduced in mutant bone marrow

♀ • frequency of monocytic/granulocytic precursors (myeloid CFUs) is significantly reduced compared to wild-type bone marrow

decreased neutrophil cell number ( J:92639 )

♀ • total leukocyte numbers are not significantly altered compared to wild-type, but significantly reduced peripheral PMN frequency in blood is observed in mutants

decreased follicular B cell number ( J:69477 )

♀ • decrease in IgD^hi IgM^lo mature follicular B cells

abnormal neutrophil physiology ( 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

impaired neutrophil phagocytosis ( J:92639 )

♀ • phagocytic ability of PMNs is somewhat lower, but not significantly, compared to wild-type

abnormal macrophage physiology ( 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

digestive/alimentary system

increased susceptibility to induced colitis ( J:92639 )

♀ • 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

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:128518 )

♀ • in Salmonella typhimurium-infected mice

cellular

impaired neutrophil phagocytosis ( J:92639 )

♀ • phagocytic ability of PMNs is somewhat lower, but not significantly, compared to wild-type

Genotype
MGI:3687754

hm3

• Allelic Composition: Btk^xid/Btk^xid
• Genetic Background: CBA/HN-Btk^xid

immune system

decreased B cell proliferation ( J:81429 )

♀ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

♀ • Background Sensitivity: proliferative response in B cells from females is drastically lower than in cells from female mutants on CBA/HN * DBA/2N background

abnormal lymphopoiesis ( J:7981 )

♀ • incidence of small lymphocytes is slightly lower, but absolute population is not, compared to controls

decreased B cell number ( J:81429 )

♀ • spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls

♀ • Background Sensitivity: numbers (22%) are less than female mutants on CBA/HN * DBA/2N background (40%)

♀ • incidence of B lymphocytes is slightly lower, but absolute population is not, compared to controls

abnormal pre-B cell morphology ( J:7981 )

♀ • incidence of pre-B cells is slightly reduced, but absolute population is comparable to controls

decreased splenocyte number ( J:81429 )

♀ • number of nucleated spleen cells (~60 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)

♀ • Background Sensitivity: females have significantly less than females on the CBA/HN * DBA/2N background which have (~90 x 10⁶/spleen)

autoimmune response ( J:125114 )

♀ • mice do not develop autoantibodies (anti-dsDNA or any IgG antinuclear autoantibodies)

hematopoietic system

decreased B cell proliferation ( J:81429 )

♀ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

♀ • Background Sensitivity: proliferative response in B cells from females is drastically lower than in cells from female mutants on CBA/HN * DBA/2N background

abnormal lymphopoiesis ( J:7981 )

♀ • incidence of small lymphocytes is slightly lower, but absolute population is not, compared to controls

abnormal bone marrow cell number ( J:7981 )

♀ • number of nucleated cells is higher in mutants than in controls

decreased B cell number ( J:81429 )

♀ • spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls

♀ • Background Sensitivity: numbers (22%) are less than female mutants on CBA/HN * DBA/2N background (40%)

♀ • incidence of B lymphocytes is slightly lower, but absolute population is not, compared to controls

abnormal pre-B cell morphology ( J:7981 )

♀ • incidence of pre-B cells is slightly reduced, but absolute population is comparable to controls

decreased splenocyte number ( J:81429 )

♀ • number of nucleated spleen cells (~60 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)

♀ • Background Sensitivity: females have significantly less than females on the CBA/HN * DBA/2N background which have (~90 x 10⁶/spleen)

cellular

decreased B cell proliferation ( J:81429 )

♀ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

♀ • Background Sensitivity: proliferative response in B cells from females is drastically lower than in cells from female mutants on CBA/HN * DBA/2N background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
X-linked agammaglobulinemia		DOID:14179	OMIM:300755	J:81429

Genotype
MGI:3814825

hm4

• Allelic Composition: Btk^xid/Btk^xid
• Genetic Background: involves: C57BL/6 * CBA

immune system

immune system phenotype ( J:113083 )

♀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)

Genotype
MGI:3687751

hm5

• Allelic Composition: Btk^xid/Btk^xid
• Genetic Background: involves: CBA/HN * DBA/2N

hematopoietic system

decreased B cell number ( J:81429 )

♀ • spleens from females have ~40% immunoglobulin-bearing cells compared to ~50% in controls

♀ • Background Sensitivity: numbers are greater in female mutants on CBA * C57BL/6 background (40%) than females on CBA/HN background (22%)

spleen hypoplasia ( J:81429 )

♀ • number of nucleated spleen cells (~90 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)

♀ • 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)

abnormal B cell physiology ( 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

abnormal B cell proliferation ( J:81429 )

♀ • B cells show response to LPS and poly I:C similar to wild-type cells

♀ • Background Sensitivity: proliferative response in B cells from females is much higher than in cells from female mutants on CBA/HN background

immune system

decreased B cell number ( J:81429 )

♀ • spleens from females have ~40% immunoglobulin-bearing cells compared to ~50% in controls

♀ • Background Sensitivity: numbers are greater in female mutants on CBA * C57BL/6 background (40%) than females on CBA/HN background (22%)

spleen hypoplasia ( J:81429 )

♀ • number of nucleated spleen cells (~90 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)

♀ • 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)

abnormal B cell physiology ( 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

abnormal B cell proliferation ( J:81429 )

♀ • B cells show response to LPS and poly I:C similar to wild-type cells

♀ • Background Sensitivity: proliferative response in B cells from females is much higher than in cells from female mutants on CBA/HN background

cellular

abnormal B cell proliferation ( J:81429 )

♀ • B cells show response to LPS and poly I:C similar to wild-type cells

♀ • Background Sensitivity: proliferative response in B cells from females is much higher than in cells from female mutants on CBA/HN background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
X-linked agammaglobulinemia		DOID:14179	OMIM:300755	J:81429

Genotype
MGI:4453853

cx6

• Allelic Composition: Btk^xid/Btk^xid; Ikzf3^tm1Kge/Ikzf3^tm1Kge
• Genetic Background: involves: 129S4/SvJae * CBA/CaHN

hematopoietic system

decreased follicular B cell number ( J:69477 )

♀ • decrease in IgD^hi IgM^lo mature follicular B cells, similar to that seen in single homozygous Btk mutant mice

♀ • however, normal numbers of marginal zone B cells are observed

immune system

decreased follicular B cell number ( J:69477 )

♀ • decrease in IgD^hi IgM^lo mature follicular B cells, similar to that seen in single homozygous Btk mutant mice

♀ • however, normal numbers of marginal zone B cells are observed

Genotype
MGI:4453854

cx7

• Allelic Composition: Btk^xid/Y; Ikzf3^tm1Kge/Ikzf3^tm1Kge
• Genetic Background: involves: 129S4/SvJae * CBA/CaHN

hematopoietic system

decreased follicular B cell number ( J:69477 )

♂ • decrease in IgD^hi IgM^lo mature follicular B cells, similar to that seen in single homozygous Btk mutant mice

♂ • however, normal numbers of marginal zone B cells are observed

immune system

decreased follicular B cell number ( J:69477 )

♂ • decrease in IgD^hi IgM^lo mature follicular B cells, similar to that seen in single homozygous Btk mutant mice

♂ • however, normal numbers of marginal zone B cells are observed

Genotype
MGI:3836568

cx8

• Allelic Composition: Btk^xid/?; Tg(IGH-Btk)1Witt/0
• Genetic Background: involves: BALB/c * C3H * C57BL/6 * CBA/N

immune system

decreased B cell proliferation ( J:108696 )

• less sensitive to anti-IgM induced proliferation compared to wild-type controls

decreased B-1 B cell number ( J:108696 )

• 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

decreased IgG3 level ( J:108696 )

• basal serum IgG3 levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene

decreased IgM level ( J:108696 )

• 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

decreased B cell proliferation ( J:108696 )

• less sensitive to anti-IgM induced proliferation compared to wild-type controls

decreased B-1 B cell number ( J:108696 )

• 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

decreased IgG3 level ( J:108696 )

• basal serum IgG3 levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene

decreased IgM level ( J:108696 )

• 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

cellular

decreased B cell proliferation ( J:108696 )

• less sensitive to anti-IgM induced proliferation compared to wild-type controls

Genotype
MGI:3836569

cx9

• Allelic Composition: Btk^xid/?; Tg(IGH-Btk)1Witt/Tg(IGH-Btk)1Witt
• Genetic Background: involves: BALB/c * C3H * C57BL/6 * CBA/N

immune system

decreased B cell proliferation ( J:108696 )

• less sensitive to anti-IgM induced proliferation compared to wild-type controls but more responsive than mutant mice hemizygous for the transgene

decreased B-1 B cell number ( J:108696 )

• 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

decreased IgG3 level ( J:108696 )

• basal serum IgG3 levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene

decreased IgM level ( J:108696 )

• 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

decreased B cell proliferation ( J:108696 )

• less sensitive to anti-IgM induced proliferation compared to wild-type controls but more responsive than mutant mice hemizygous for the transgene

decreased B-1 B cell number ( J:108696 )

• 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

decreased IgG3 level ( J:108696 )

• basal serum IgG3 levels are decreased compared to wild-type controls but increased compared to mutant mice not carrying the transgene

decreased IgM level ( J:108696 )

• 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

cellular

decreased B cell proliferation ( J:108696 )

• less sensitive to anti-IgM induced proliferation compared to wild-type controls but more responsive than mutant mice hemizygous for the transgene

Genotype
MGI:5314647

cx10

• Allelic Composition: Btk^xid/?; Ptpn6^me/Ptpn6^me
• Genetic Background: involves: C57BL/6J * CBA/N * NFS

mortality/aging

premature death ( J:30994 )

• Background Sensitivity: life span about 8 weeks whereas on a C57BL/6 background survival is about 3 weeks

growth/size/body

decreased body weight ( J:30994 )

• weigh about 66% of control weight

limbs/digits/tail

absent limbs ( J:30994 )

• autoamputation of 2-3 extremities by 8 weeks of age

integument

abnormal skin condition ( J:30994 )

• cutaneous granulomatous lesions at 8 weeks

immune system

increased splenocyte proliferation ( J:30994 )

• lack of stimulatory effect of ConA

increased IgM level ( J:30994 )

• increased secretion by splenocytes in culture

• serum levels considerably lower than Ptpn6^me/me controls

increased autoantibody level ( J:30994 )

• very slightly elevated relative to controls

cellular

increased splenocyte proliferation ( J:30994 )

• lack of stimulatory effect of ConA

hematopoietic system

increased splenocyte proliferation ( J:30994 )

• lack of stimulatory effect of ConA

increased IgM level ( J:30994 )

• increased secretion by splenocytes in culture

• serum levels considerably lower than Ptpn6^me/me controls

Genotype
MGI:3687750

ot11

• Allelic Composition: Btk^xid/Y
• Genetic Background: CBA/HN-Btk^xid

immune system

decreased B cell proliferation ( J:81429 )

♂ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

decreased B cell number ( J:81429 )

♂ • spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls

decreased splenocyte number ( J:81429 )

♂ • number of nucleated spleen cells (~60 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)

hematopoietic system

decreased B cell proliferation ( J:81429 )

♂ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

decreased B cell number ( J:81429 )

♂ • spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls

decreased splenocyte number ( J:81429 )

♂ • number of nucleated spleen cells (~60 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)

cellular

decreased B cell proliferation ( J:81429 )

♂ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
X-linked agammaglobulinemia		DOID:14179	OMIM:300755	J:81429

Genotype
MGI:3687752

ot12

• Allelic Composition: Btk^xid/Y
• Genetic Background: involves: CBA/HN * DBA/2N

hematopoietic system

decreased B cell proliferation ( J:81429 )

♂ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

♂ • proliferative response occurs slightly later and is much lower in males than in females

decreased B cell number ( J:81429 )

♂ • spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls

spleen hypoplasia ( J:81429 )

♂ • number of nucleated spleen cells (~50 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)

immune system

decreased B cell proliferation ( J:81429 )

♂ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

♂ • proliferative response occurs slightly later and is much lower in males than in females

decreased B cell number ( J:81429 )

♂ • spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls

spleen hypoplasia ( J:81429 )

♂ • number of nucleated spleen cells (~50 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)

cellular

decreased B cell proliferation ( J:81429 )

♂ • cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells

♂ • proliferative response occurs slightly later and is much lower in males than in females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
X-linked agammaglobulinemia		DOID:14179	OMIM:300755	J:81429

Genotype
MGI:3836566

ot13

• Allelic Composition: Btk^xid/?
• Genetic Background: involves: BALB/c * CBA/N

immune system

decreased B cell proliferation ( J:108696 )

• no increase in proliferation is seen after BCR cross-linking

decreased mature B cell number ( J:108696 )

• the frequency and number of B cells are reduced in the spleen

decreased B-1 B cell number ( J:108696 )

• drastic reduction in the percentage of CD5+B220+ cells in the peritoneum

decreased IgG3 level ( J:108696 )

decreased IgM level ( J:108696 )

• 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

decreased B cell proliferation ( J:108696 )

• no increase in proliferation is seen after BCR cross-linking

decreased mature B cell number ( J:108696 )

• the frequency and number of B cells are reduced in the spleen

decreased B-1 B cell number ( J:108696 )

• drastic reduction in the percentage of CD5+B220+ cells in the peritoneum

decreased IgG3 level ( J:108696 )

decreased IgM level ( J:108696 )

• 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

cellular

decreased B cell proliferation ( J:108696 )

• no increase in proliferation is seen after BCR cross-linking