Phenotypes associated with this allele

• Allele Symbol: Itgb1^tm1Efu
• Allele Name: targeted mutation 1, Elaine Fuchs
• Allele ID: MGI:1926499
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Itgb1^tm1Efu/Itgb1^tm1Efu Tg(KRT14-cre)1Efu/0	involves: 129X1/SvJ	MGI:2448680
cn2	Itgb1^tm1Efu/Itgb1^tm1Efu Tg(ATP6V1B1-cre)45Rnel/0	involves: 129X1/SvJ * C57BL/6	MGI:4868737
cn3	Itgb1^tm1Efu/Itgb1^tm1Efu Tg(Cryaa-cre)10Mlr/?	involves: 129X1/SvJ * C57BL/6	MGI:3715212
cn4	Itgb1^tm1Efu/Itgb1^tm1Efu Tg(Vil1-cre)997Gum/0	involves: 129X1/SvJ * C57BL/6J * SJL	MGI:3703443
cn5	Itgb1^tm1Efu/Itgb1^tm1Efu Tg(NPHS2-cre)295Lbh/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:5142307

Genotype
MGI:2448680

cn1

• Allelic Composition: Itgb1^tm1Efu/Itgb1^tm1Efu; Tg(KRT14-cre)1Efu/0
• Genetic Background: involves: 129X1/SvJ

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:65039 )

• usually die within a few hours of birth

integument

abnormal hair follicle development ( J:65039 )

• hair follicle keratinocytes fail to remodel basement membrane and invaginate into the dermis

decreased hair follicle number ( J:65039 )

• developing hair follicles are scarce, although a few mature hair follicles, most likely guard hairs, are detected

abnormal epidermal layer morphology ( J:65039 )

• epidermal proliferation is inhibited, however a spatial and temporal program of terminal differentiation does occur

abnormal epidermis stratum basale morphology ( J:65039 )

• basal cells of the epidermis are flat and the nucleus is oriented parallel to the basement membrane

thin epidermis ( J:65039 )

• epidermis consists of a flattened basal layer and only one or two layers of suprabasal layers before the stratum corneum

dermal-epidermal separation ( J:65039 )

• many areas of skin exhibit separations at the dermal-epidermal junction, such that in severely affected areas, the epidermis is detached entirely from the dermis

blistering ( J:65039 )

• severe skin blistering

abnormal skin condition ( J:65039 )

• exhibit separation of the dermal-epidermal junction upon mechanical trauma, indicating fragile skin, however do not display denuding

thin skin ( J:65039 )

• thin and fragile

cellular

abnormal basement membrane morphology ( J:65039 )

• basement membrane assembly/organization is impaired, leading to a loss of extracellular matrix and hemidesmosomes

• skin shows discontinuity of the lamina densa

Genotype
MGI:4868737

cn2

• Allelic Composition: Itgb1^tm1Efu/Itgb1^tm1Efu; Tg(ATP6V1B1-cre)45Rnel/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6

homeostasis/metabolism

decreased circulating bicarbonate level ( J:167156 )

metabolic acidosis ( J:167156 )

• metabolic acidosis

renal tubular acidosis ( J:167156 )

increased urine pH ( J:167156 )

renal/urinary system

renal tubular acidosis ( J:167156 )

increased urine pH ( J:167156 )

abnormal kidney cortex morphology ( J:167156 )

• in the kidney cortex, beta-intercalated cells are replaced with alpha-intercalated cells unlike in wild-type mice

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:167156 )

N • mice exhibit normal compound action potentials

Genotype
MGI:3715212

cn3

• Allelic Composition: Itgb1^tm1Efu/Itgb1^tm1Efu; Tg(Cryaa-cre)10Mlr/?
• Genetic Background: involves: 129X1/SvJ * C57BL/6

vision/eye

abnormal lens epithelium morphology ( J:122566 )

• at E16.5, mild lens epithelial elongation is observed

• at birth, lens epithelium is missing and remaining epithelial cells are abnormally elongated

• at birth, epithelial cells in the lens are lost by apoptosis

abnormal lens fiber morphology ( J:122566 )

• at birth, lens fibers are highly vacuolated and disintegrating

aphakia ( J:122566 )

• adult mice have little to no lens material

microphthalmia ( J:122566 )

• microphthalmia in adults

• however, mice are born with normal sized eyes

Genotype
MGI:3703443

cn4

• Allelic Composition: Itgb1^tm1Efu/Itgb1^tm1Efu; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * SJL

Crypt hyperplasia and dysplasia and villous enlargement in Itgb1^tm1Efu/Itgb1^tm1Efu Tg(Vil1-cre)997Gum/0 mice

mortality/aging

postnatal lethality, complete penetrance ( J:119155 )

• die between P7 and P14 from severe malnutrition

growth/size/body

decreased body weight ( J:119155 )

• by P4, mutants are less than half the body weight of controls

digestive/alimentary system

abnormal intestine morphology ( J:119155 )

• expansion of the intestinal stroma, muscularis, and extracellular matrix

abnormal intestinal epithelium morphology ( J:119155 )

• mutants exhibit an increase in intestinal epithelial cell proliferation in the crypts with dysplasia and polyps, resulting in an expanded epithelium

• the small intestinal epithelium shows a defective microvillus brush border on the apical surfaces of the villous enterocytes

abnormal enterocyte morphology ( J:119155 )

• the intestinal epithelium shows large lipid inclusions within the villous enterocytes that are not seen in controls

• the intestinal microvilli are diminished in size and poorly formed, indicatiang defective enterocyte differentiation

abnormal crypts of Lieberkuhn morphology ( J:119155 )

• intestinal crypt and villi expansion, enlargement, and dysplasia at P16

• crypt hyperplasia is most severe in the distal small intestine, proximal large intestine, and cecum

abnormal large intestine morphology ( J:119155 )

• proximal large intestine is larger in external diameter than in controls

abnormal small intestine morphology ( J:119155 )

• distal small intestine is larger in external diameter than in controls

intestine polyps ( J:119155 )

• multiple juvenile-like polyps in the small intestinal mucosa

abnormal intestinal absorption ( J:119155 )

• although mutants can feed, they are malnourished due to intestinal epithelium defects

steatorrhea ( J:119155 )

• fat malabsorption as indicated by the presence of large fat droplets in the intestinal contents

homeostasis/metabolism

steatorrhea ( J:119155 )

• fat malabsorption as indicated by the presence of large fat droplets in the intestinal contents

abnormal circulating lipid level ( J:119155 )

• total serum lipid levels are reduced

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:119155 )

• intestinal crypt and villi expansion, enlargement, and dysplasia at P16

• crypt hyperplasia is most severe in the distal small intestine, proximal large intestine, and cecum

Genotype
MGI:5142307

cn5

• Allelic Composition: Itgb1^tm1Efu/Itgb1^tm1Efu; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

mortality/aging

premature death ( J:135414 )

• only 10% of mice survived to 6 weeks of age

• 90% of mice were euthanized at 4-5 weeks of age due to end stage renal failure and nephrotic syndrome

behavior/neurological

decreased locomotor activity ( J:135414 )

• mice become less physically active at 3 weeks of age

growth/size/body

decreased body size ( J:135414 )

• at 6 weeks of age, mice are smaller than control littermates

homeostasis/metabolism

edema ( J:135414 )

• mice develop severe edema at 3 weeks of age

increased urine protein level ( J:135414 )

• mice develop severe proteinuria by 6 weeks of age

albuminuria ( J:135414 )

• albuminuria is already evident at P1

• marked albuminuria is noted at 6 weeks of age

renal/urinary system

increased podocyte apoptosis ( J:135414 )

• a significant increase in podocyte apoptosis is detected at P10 and P21 by TUNEL analysis

• at P21, mice exhibit about one-third of the podocyte number found in control littermates, as quantified in EM sections

increased urine protein level ( J:135414 )

• mice develop severe proteinuria by 6 weeks of age

albuminuria ( J:135414 )

• albuminuria is already evident at P1

• marked albuminuria is noted at 6 weeks of age

abnormal kidney morphology ( J:135414 )

• mice develop end stage kidney disease with pathological changes in the glomeruli and tubulo-interstitium

abnormal renal glomerular capsule morphology ( J:135414 )

• at 6 weeks of age, many Bowmans capsules are either empty or contain partially degenerated glomeruli

podocyte foot process effacement ( J:135414 )

• foot process effacement is first noted at E15.5

• extensive foot process effacement is noted at P10 and progresses by P21

abnormal renal glomerulus basement membrane morphology ( J:135414 )

• early segmental splitting of the glomerular basement membrane (GBM) is first noted at P10 and progresses by P21

• however, normal GBM morphogenesis is noted at E15.5 and at P1

abnormal renal glomerulus morphology ( J:135414 )

• at P21, mice exhibit degeneration of the capillary loops and mesangium with little glomerulosclerosis

• at 6 weeks of age, mice exhibit dilated glomerular capillaries and glomerular disintegration

abnormal glomerular capillary morphology ( J:135414 )

• by P21, mice exhibit degeneration of the capillary loops

• however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1

dilated glomerular capillary ( J:135414 )

• at P10, some glomeruli display segmentally "ballooned" capillary lumens; more "ballooned" capillary loops are noted at 3 weeks of age

• at 6 weeks of age, mice exhibit dilated glomerular capillaries

increased mesangial cell number ( J:135414 )

• mesangium hypercellularity is observed by 3 weeks of age

expanded mesangial matrix ( J:135414 )

• increased mesangial matrix with focal defects is noted at 3 weeks, indicating mesangial injury

mesangiolysis ( J:135414 )

• multiple cytoplasmic vacuoles are first noted in mesangial cells at P10

• by P21, mice exhibit degeneration of the mesangium with little glomerulosclerosis

abnormal renal tubule epithelium morphology ( J:135414 )

• at P10, mice exhibit multiple cytoplasmic vacuoles within the tubular epithelial cells

• flattened epithelial cells with extensive proteinaceous tubular casts are noted at 6 weeks of age

small kidney ( J:135414 )

• at 6 weeks of age, end stage kidneys are smaller than those of age-matched control mice

dilated renal tubule ( J:135414 )

• dilated renal tubules containing hyaline material are observed at 6 weeks of age

• tubular dilatation is first evident at P10 and increased by 3 weeks of age

renal cast ( J:135414 )

• extensive proteinaceous tubular casts are noted at 6 weeks of age

pale kidney ( J:135414 )

• at 6 weeks of age, end stage kidneys are paler than those of age-matched control mice

cardiovascular system

abnormal glomerular capillary morphology ( J:135414 )

• by P21, mice exhibit degeneration of the capillary loops

• however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1

dilated glomerular capillary ( J:135414 )

• at P10, some glomeruli display segmentally "ballooned" capillary lumens; more "ballooned" capillary loops are noted at 3 weeks of age

• at 6 weeks of age, mice exhibit dilated glomerular capillaries

cellular

increased mesangial cell number ( J:135414 )

• mesangium hypercellularity is observed by 3 weeks of age

increased podocyte apoptosis ( J:135414 )

• a significant increase in podocyte apoptosis is detected at P10 and P21 by TUNEL analysis

• at P21, mice exhibit about one-third of the podocyte number found in control littermates, as quantified in EM sections