Btk<xid> Spontaneous Allele Detail MGI Mouse (MGI:1856317)

Btk^xid
Spontaneous Allele Detail

Nomenclature

Symbol:	Btk^xid
Name:	Bruton agammaglobulinemia tyrosine kinase; X linked immune deficiency
MGI ID:	MGI:1856317
Synonyms:	xid
Gene:	Btk Location: ChrX:131076875-131118109 bp, - strand Genetic Position: ChrX, 51.0 cM

Mutation
origin

Strain of Origin:

CBA/HN

Mutation
description

Allele Type:	Spontaneous
Mutation:	Single point mutation
	The C to T transition point mutation at position 219 is predicted to change amino acid 28 from an arginine to a cysteine in the encoded protein. (J:13209)
Inheritance:	Recessive

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 2 strains available Cell Lines: 0 lines available
Carrying any Btk Mutation:	7 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	hm2	hm3	hm4	hm5	tg6	tg7	ot8	ot9	ot10
digestive/alimentary system			√
increased susceptibility to induced colitis			√
		hm1	hm2	hm3	hm4	hm5	tg6	tg7	ot8	ot9	ot10
hematopoietic system		√	√	√		√	√	√	√	√	√
decreased neutrophil cell number			√
impaired myelopoiesis			√
decreased B cell number				√		√			√	√
decreased transitional stage B cell number		√
decreased mature B cell number											√
decreased B-1 B cell number							√	√			√
abnormal lymphopoiesis				√
abnormal pre-B cell morphology				√
abnormal B cell proliferation						√
decreased B cell proliferation				√			√	√	√	√	√
abnormal bone marrow cell number				√
decreased splenocyte number				√					√
spleen hypoplasia						√				√
		hm1	hm2	hm3	hm4	hm5	tg6	tg7	ot8	ot9	ot10
immune system		√	√	√	N	√	√	√	√	√	√
immune system phenotype					N
increased susceptibility to induced colitis			√
decreased neutrophil cell number			√
impaired myelopoiesis			√
abnormal macrophage physiology			√
abnormal neutrophil physiology			√
impaired neutrophil phagocytosis			√
decreased acute inflammation			√
decreased B cell number				√		√			√	√
decreased transitional stage B cell number		√
decreased mature B cell number											√
decreased B-1 B cell number							√	√			√
abnormal lymphopoiesis				√
abnormal pre-B cell morphology				√
abnormal B cell proliferation						√
decreased B cell proliferation				√			√	√	√	√	√
decreased splenocyte number				√					√
autoimmune response				√
decreased susceptibility to experimental autoimmune encephalomyelitis			√
spleen hypoplasia						√				√
abnormal B cell physiology						√
decreased IgG3 level							√	√			√
decreased IgM level							√	√			√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Btk^xid/Btk^xid	B6.CBA-Btk^xid
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	Allelic Composition	Genetic Background
hm2	Btk^xid/Btk^xid	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 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 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 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 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 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 hematopoietic system 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 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 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
Genotype	Allelic Composition	Genetic Background
hm3	Btk^xid/Btk^xid	CBA/HN-Btk^xid
immune system decreased B cell number (J:81429) Background Sensitivity: numbers (22%) are less than female mutants on CBA/HN * DBA/2N background (40%) spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls incidence of B lymphocytes is slightly lower, but absolute population is not, compared to controls abnormal lymphopoiesis (J:7981) incidence of small lymphocytes is slightly lower, but absolute population is not, compared to controls decreased B cell proliferation (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 cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells 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) Background Sensitivity: females have significantly less than females on the CBA/HN * DBA/2N background which have (~90 x 10⁶/spleen) number of nucleated spleen cells (~60 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen) autoimmune response (J:125114) mice do not develop autoantibodies (anti-dsDNA or any IgG antinuclear autoantibodies) hematopoietic system decreased B cell number (J:81429) Background Sensitivity: numbers (22%) are less than female mutants on CBA/HN * DBA/2N background (40%) spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls incidence of B lymphocytes is slightly lower, but absolute population is not, compared to controls abnormal lymphopoiesis (J:7981) incidence of small lymphocytes is slightly lower, but absolute population is not, compared to controls decreased B cell proliferation (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 cultured B cells show little response to B-cell mitogens LPS and poly I:C in comparison to wild-type cells abnormal pre-B cell morphology (J:7981) incidence of pre-B cells is slightly reduced, but absolute population is comparable to controls abnormal bone marrow cell number (J:7981) number of nucleated cells is higher in mutants than in controls decreased splenocyte number (J:81429) Background Sensitivity: females have significantly less than females on the CBA/HN * DBA/2N background which have (~90 x 10⁶/spleen) number of nucleated spleen cells (~60 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)
Genotype	Allelic Composition	Genetic Background
hm4	Btk^xid/Btk^xid	involves: C57BL/6 * CBA
immune system immune system phenotype (J:113083) 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	Allelic Composition	Genetic Background
hm5	Btk^xid/Btk^xid	involves: CBA/HN * DBA/2N
hematopoietic system decreased B cell number (J:81429) Background Sensitivity: numbers are greater in female mutants on CBA * C57BL/6 background (40%) than females on CBA/HN background (22%) spleens from females have ~40% immunoglobulin-bearing cells compared to ~50% in controls abnormal B cell proliferation (J:81429) Background Sensitivity: proliferative response in B cells from females is much higher than in cells from female mutants on CBA/HN background B cells show response to LPS and poly I:C similar to wild-type cells spleen hypoplasia (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) number of nucleated spleen cells (~90 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen) immune system decreased B cell number (J:81429) Background Sensitivity: numbers are greater in female mutants on CBA * C57BL/6 background (40%) than females on CBA/HN background (22%) spleens from females have ~40% immunoglobulin-bearing cells compared to ~50% in controls spleen hypoplasia (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) number of nucleated spleen cells (~90 x 10⁶/spleen) is significantly lower than in controls (~120 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) Background Sensitivity: proliferative response in B cells from females is much higher than in cells from female mutants on CBA/HN background B cells show response to LPS and poly I:C similar to wild-type cells
Genotype	Allelic Composition	Genetic Background
tg6	Btk^xid/? Tg(IGH-Btk)1Witt/0	involves: BALB/c * C3H * C57BL/6 * CBA/N
immune system 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 B cell proliferation (J:108696) less sensitive to anti-IgM induced proliferation compared 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-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 B cell proliferation (J:108696) less sensitive to anti-IgM induced proliferation compared to wild-type controls
Genotype	Allelic Composition	Genetic Background
tg7	Btk^xid/? Tg(IGH-Btk)1Witt/Tg(IGH-Btk)1Witt	involves: BALB/c * C3H * C57BL/6 * CBA/N
immune system 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 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 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-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 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	Allelic Composition	Genetic Background
ot8	Btk^xid/Y	CBA/HN-Btk^xid
immune system decreased B cell number (J:81429) spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls 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 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 number (J:81429) spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls 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 splenocyte number (J:81429) number of nucleated spleen cells (~60 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)
Genotype	Allelic Composition	Genetic Background
ot9	Btk^xid/Y	involves: CBA/HN * DBA/2N
hematopoietic system decreased B cell number (J:81429) spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls 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 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 number (J:81429) spleens have only ~22% immunoglobulin-bearing cells compared to ~50% in controls 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 spleen hypoplasia (J:81429) number of nucleated spleen cells (~50 x 10⁶/spleen) is significantly lower than in controls (~120 x 10⁶/spleen)
Genotype	Allelic Composition	Genetic Background
ot10	Btk^xid/?	involves: BALB/c * CBA/N
immune system 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 B cell proliferation (J:108696) no increase in proliferation is seen after BCR cross-linking 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 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 B cell proliferation (J:108696) no increase in proliferation is seen after BCR cross-linking

References

Original:	J:6296 Berning AK et al., "Mapping of the X-linked immune deficiency mutation (xid) of CBA/N mice." J Immunol 1980 Apr;124(4):1875-7
All:	129 reference(s)

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