Phenotypes associated with this allele

• Allele Symbol: B4galt1^tm1Yiw
• Allele Name: targeted mutation 1, Yoichiro Iwakura
• Allele ID: MGI:2450889
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	B4galt1^tm1Yiw/B4galt1^tm1Yiw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6306320
hm2	B4galt1^tm1Yiw/B4galt1^tm1Yiw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3620087
ht3	B4galt1^tm1Yiw/B4galt1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6306325
ht4	B4galt1^tm1Yiw/B4galt1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3620088

Genotype
MGI:6306320

hm1

• Allelic Composition: B4galt1^tm1Yiw/B4galt1^tm1Yiw
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

renal/urinary system

albuminuria ( J:117891 )

hematuria ( J:117891 )

• hematuria is seen in some mice and increases with age

abnormal renal glomerulus morphology ( J:117891 )

• glomerulomegaly

• acellular eosinophilic lesions are seen near the vascular pole of the glomerulus

• glomerular lesions are classified into minor glomerular abnormality, segmental lesion and global lesion

• about 75% of glomeruli are affected at 8-13 weeks of age, with increased global lesions with age

glomerulonephritis ( J:117891 )

• glomeruli show predominantly IgA, and some IgG, IgM, and C3 mesangial deposits, with deposits specifically detected in the paramesangial areas

abnormal glomerular mesangium morphology ( J:117891 )

• Mason's trichrome staining suggests deposition of immune complexes in the mesangial area

• mice exhibit predominantly IgA, and some IgG, IgM, and C3 mesangial deposits

expanded mesangial matrix ( J:117891 )

glomerulosclerosis ( J:117891 )

• glomerular sclerosis is seen at 8 weeks and progresses with age

immune system

increased IgA level ( J:117891 )

• glomeruli show predominantly IgA mesangial deposits, with deposits specifically detected in the paramesangial areas

• serum IgA levels increase with age with increased polymeric forms and completely absent beta4-galactosylation and sialylation of the N-glycans on the serum IgA

abnormal IgM level ( J:117891 )

• serum IgM levels are about 2-fold higher than in heterozygous mice at 12-13 weeks of age but are about half of that in heterozygotes at 24-28 weeks of age

• glomeruli show some IgM mesangial deposits

glomerulonephritis ( J:117891 )

• glomeruli show predominantly IgA, and some IgG, IgM, and C3 mesangial deposits, with deposits specifically detected in the paramesangial areas

homeostasis/metabolism

albuminuria ( J:117891 )

hematuria ( J:117891 )

• hematuria is seen in some mice and increases with age

hematopoietic system

increased IgA level ( J:117891 )

• glomeruli show predominantly IgA mesangial deposits, with deposits specifically detected in the paramesangial areas

• serum IgA levels increase with age with increased polymeric forms and completely absent beta4-galactosylation and sialylation of the N-glycans on the serum IgA

abnormal IgM level ( J:117891 )

• serum IgM levels are about 2-fold higher than in heterozygous mice at 12-13 weeks of age but are about half of that in heterozygotes at 24-28 weeks of age

• glomeruli show some IgM mesangial deposits

neoplasm

neoplasm ( J:117891 )

N • growth rate of the strongly immunogenic colon carcinoma MC38 tumor cells is unaffected

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
IgA glomerulonephritis		DOID:2986	OMIM:161950	J:117891

Genotype
MGI:3620087

hm2

• Allelic Composition: B4galt1^tm1Yiw/B4galt1^tm1Yiw
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

premature death ( J:40026 )

• only 20% survive beyond 16 weeks of age

postnatal lethality, incomplete penetrance ( J:40026 )

• about half die before 4 weeks of age

immune system

enlarged spleen ( J:106669 )

increased leukocyte cell number ( J:106669 )

• total white blood cell counts in the peripheral blood are increased 2.2-fold

• however, the number of colony forming units formed by bone marrow cells in the presence of G-CSF or IL3 are similar to wild-type

increased neutrophil cell number ( J:106669 )

• neutrophil counts are increased 2.3-fold

increased lymphocyte cell number ( J:106669 )

• lymphocyte counts are increased 2.5-fold

abnormal leukocyte physiology ( J:106669 )

• expression of selectin ligand and binding of P-selectin to splenic monocytes is severely reduced; however lymphocyte homing to peripheral lymph nodes is normal

impaired macrophage chemotaxis ( J:89125 )

• 3 and 6 days after injury macrophage infiltration is decreased

abnormal neutrophil physiology ( J:106669 )

• expression of selectin ligand and binding of P-selectin to splenic neutrophils is severely reduced

impaired neutrophil recruitment ( J:89125 )

• 6 and 24 hours after injury neutrophil infiltration is reduced and binding of infiltrated neutrophils to P-selectin is weak compared to binding of heterozygous controls

decreased acute inflammation ( J:106669 )

• zymosan-induced ear swelling is significantly reduced and neutrophil trafficking into the ear is not induced

decreased susceptibility to type IV hypersensitivity reaction ( J:106669 )

• contact hypersensitivity induced by 2,4,6-trinitrochlorobenzene in the ear lobe is partially suppressed and neutrophil trafficking is also reduced

• delayed type hypersensitivity induced by methylated bovine serum albumin in the foot pad is partially suppressed and leukocyte infiltration into the dermis of the footpad is blocked

cardiovascular system

abnormal physiological neovascularization ( J:89125 )

• 6 days after injury vascular density at the wound site is decreased

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:40026 )

• increased proliferation of epithelial cells

abnormal small intestine morphology ( J:40026 )

• differentiation of villi is abnormal with premature expression of maltase and sucrase-isomaltase, increased maltase and isomaltase activities, decreased lactase activity, and delayed or absent sucrase activity

abnormal small intestine crypts of Lieberkuhn morphology ( J:40026 )

• in the small intestine the crypts are enlarged 3- to 4-fold and the mitotic index is increased about 4-fold

growth/size/body

decreased body weight ( J:40026 )

• at 4 weeks of age average body weight is 60-70% that of wild-type mice

postnatal growth retardation ( J:40026 )

enlarged spleen ( J:106669 )

reproductive system

decreased litter size ( J:40026 )

• litter sizes from crosses of homozygous females to heterozygous males or heterozygous females to homozygous males are reduced compared to wild-type crosses

hematopoietic system

enlarged spleen ( J:106669 )

extramedullary hematopoiesis ( J:106669 )

• erythroid precursors, granulocytes and megakaryocytes are seen in the spleen and liver

abnormal proerythroblast morphology ( J:106669 )

• number of colony forming units formed by bone marrow cells in the presence of EPO is increased

decreased erythrocyte cell number ( J:106669 )

• slight but significant

decreased hematocrit ( J:106669 )

• slight but significant

decreased hemoglobin content ( J:106669 )

• slight but significant

increased leukocyte cell number ( J:106669 )

• total white blood cell counts in the peripheral blood are increased 2.2-fold

• however, the number of colony forming units formed by bone marrow cells in the presence of G-CSF or IL3 are similar to wild-type

increased neutrophil cell number ( J:106669 )

• neutrophil counts are increased 2.3-fold

increased lymphocyte cell number ( J:106669 )

• lymphocyte counts are increased 2.5-fold

abnormal leukocyte physiology ( J:106669 )

• expression of selectin ligand and binding of P-selectin to splenic monocytes is severely reduced; however lymphocyte homing to peripheral lymph nodes is normal

impaired macrophage chemotaxis ( J:89125 )

• 3 and 6 days after injury macrophage infiltration is decreased

abnormal neutrophil physiology ( J:106669 )

• expression of selectin ligand and binding of P-selectin to splenic neutrophils is severely reduced

impaired neutrophil recruitment ( J:89125 )

• 6 and 24 hours after injury neutrophil infiltration is reduced and binding of infiltrated neutrophils to P-selectin is weak compared to binding of heterozygous controls

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:40026 )

• in the small intestine the crypts are enlarged 3- to 4-fold and the mitotic index is increased about 4-fold

abnormal milk composition ( J:40026 )

♀ • lactose is absent from the milk and females can not rear their offspring

cellular

increased mitotic index ( J:106669 )

• mitotic index is increased 4-fold in intestinal crypt epithelium

impaired macrophage chemotaxis ( J:89125 )

• 3 and 6 days after injury macrophage infiltration is decreased

homeostasis/metabolism

delayed wound healing ( J:89125 )

• 3 and 6 days after injury (full thickness excisional wounds on the dorsal skin) wound closure is delayed, the rate of re-epithelialization is reduced, macrophage infiltration is decreased, and collagen synthesis is significantly lower; however by 14 days wounds have healed to the same extent as in heterozygous controls

• 3, but not 6, days after injury chemokine expression at the wound site is reduced

• 6 and 24 hours after injury neutrophil infiltration is reduced

integument

abnormal milk composition ( J:40026 )

♀ • lactose is absent from the milk and females can not rear their offspring

abnormal epidermis stratum corneum morphology ( J:40026 )

• thickening of the horny layer is also seen in the lesions

hyperkeratosis ( J:40026 )

abnormal epidermis stratum granulosum morphology ( J:40026 )

• granular layer hyperplasia is seen in the skin lesions

abnormal epidermis stratum spinosum morphology ( J:40026 )

• prickle cell hyperplasia is seen in the skin lesions and keratohyalin granules are abnormally deposited in the prickle cell layer

acanthosis ( J:40026 )

skin lesions ( J:40026 )

• most develop severe skin lesions within a few days of birth, these lesions shed horny cells for about 2 weeks but eventually heal

Genotype
MGI:6306325

ht3

• Allelic Composition: B4galt1^tm1Yiw/B4galt1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

renal/urinary system

abnormal renal glomerulus morphology ( J:117891 )

• mice show a slight increase in segmental lesions in glomeruli

• about 75% of glomeruli exhibit minor glomerular abnormality at older (47-48 weeks) ages

Genotype
MGI:3620088

ht4

• Allelic Composition: B4galt1^tm1Yiw/B4galt1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

reproductive system

decreased litter size ( J:40026 )

• litter sizes from crosses of homozygous females to heterozygous males or heterozygous females to homozygous males are reduced compared to wild-type crosses

endocrine/exocrine glands

abnormal milk composition ( J:40026 )

♀ • lactose concentration is about 50% of wild-type

integument

abnormal milk composition ( J:40026 )

♀ • lactose concentration is about 50% of wild-type