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Allele Symbol Allele Name Allele ID |
Itgb1tm1Ref targeted mutation 1, Reinhard Fassler MGI:1926498 |
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| Summary |
14 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• alpha cells are increased in number
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• 81% of mice have alpha cells in the center of the islet
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following pIpC-induction, dendritic cells transplanted into the footpad exhibit normal drainage into lymph nodes
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• abolished in pIpC-induced mice
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• following pIpC-induction, dendritic cells fail to adhere to and migrate on a 2-D substrate unlike wild-type dendritic cells
• however, dendritic cells from pIpC-induced mice exhibit normal migration in 3D matrix
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• abolished in pIpC-induced mice
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• abolished in pIpC-induced mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• while neuronal processes from segments of the E13.5 proximal midgut penetrate a collagen matrix in the presence of GDNF, the neuron cell bodies or glial cells do not as in the case of wild-type neurons
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• enteric neural crest cells exhibit an abnormal association with neuronal processes
• beginning at E12.5, enteric neural crest cells exhibit increased aggregation and form abnormal clusters that are depend on calcium mechanisms
• in culture, enteric neural crest cells form aggregates instead of forming scattered neuronal networks as do wild-type cells
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• in mutants a severe alteration of the neuronal network rostral to the migratory front in observed
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• bundles of extrinsic neurons innervate the aganglionic segments of the colon
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• majority of newborn mutants have a distended ascending colon and caecum
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• in conditional mutants from E11.5, enteric neural crest cells show a delay in colonization of the gut; difference in distance traveled by cells in mutants and controls increases with time
• neural crest cells from mutants fail to invade the hindgut, leading to an aganglionosis of the descending colon after birth
• however, the number of enteric neural crest cells, differentiation and radial distribution of enteric neural crest cells are normal
• when transplanted into wild-type mice, enteric neural crest cells only migrate 66.5% of the distance that wild-type cells migrate
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• enteric neural crest cells exhibit an abnormal association with neuronal processes
• beginning at E12.5, enteric neural crest cells exhibit increased aggregation and form abnormal clusters that are depend on calcium mechanisms
• in culture, enteric neural crest cells form aggregates instead of forming scattered neuronal networks as do wild-type cells
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• in conditional mutants from E11.5, enteric neural crest cells show a delay in colonization of the gut; difference in distance traveled by cells in mutants and controls increases with time
• neural crest cells from mutants fail to invade the hindgut, leading to an aganglionosis of the descending colon after birth
• however, the number of enteric neural crest cells, differentiation and radial distribution of enteric neural crest cells are normal
• when transplanted into wild-type mice, enteric neural crest cells only migrate 66.5% of the distance that wild-type cells migrate
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• while neuronal processes from segments of the E13.5 proximal midgut penetrate a collagen matrix in the presence of GDNF, the neuron cell bodies or glial cells do not as in the case of wild-type neurons
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Hirschsprung's disease | DOID:10487 |
OMIM:600156 OMIM:606874 OMIM:606875 OMIM:608462 OMIM:611644 |
J:108439 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• derived cells have fewer projections
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• derived cell lines exhibit decreased binding to collagen IV
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• more derived tumor cells are arrested in G0/G1 than in Itgb1tm1Ref Tg(RIP1-Tag)2Dh controls
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• cultured cells die within a week after plating compared to Itgb1tm1Ref Tg(RIP1-Tag)2Dh derived cells
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• more derived tumor cells are arrested in G0/G1 than in Itgb1tm1Ref Tg(RIP1-Tag)2Dh controls
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• when derived cell lines are injected into nu/nu mice, metastatic nodules from do not form in the lungs and or liver as they do in wild-type mice
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• 60% of mice have an increase in the number of disseminated tumor cell emboli within lymphatic vessels near tumors compared to 7.7% in Itgb1tm1Ref Tg(RIP1-Tag)2Dh mice
• however, no metastasis is detected in mice with tumors
• tumor volume is reduced compared to that in Itgb1tm1Ref Tg(RIP1-Tag)2Dh mice
• tumor cell proliferation is significantly reduced and apoptotic rate is reduced compared to Itgb1tm1Ref Tg(RIP1-Tag)2Dh mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit progressive reduction of chondrocyte proliferation (a 25% reduction at birth, 60% reduction at 3 weeks and no proliferation at 6 weeks)
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• most mice die shortly after birth due to respiratory distress
• however, 3 of 223 mice survive
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• mice exhibit progressive reduction of chondrocyte proliferation (a 25% reduction at birth, 60% reduction at 3 weeks and no proliferation at 6 weeks)
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• at E17.5, mice exhibit reductions of the half tibia length (17.2% reduction), the distance between the growth plate and the middle of diaphysis (43.2% reduction), the length of the bone marrow zone (45% reduction) and the length of the hypertrophic zone (15% reduction) compared to wild-type mice
• at E17.5, the resting zone is increased in length by 10% compared to wild-type mice
• the growth plate is severely disorganized with large and round-shaped chondrocytes failing to glide over each other and form columns as in wild-type mice
• at 6 weeks of age, growth plates are completely disorganized and broadened
• however, the length of the proliferative zone and the total growth plate height are normal
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• at E17.5, mice exhibit 15% reduction in the length of the hypertrophic zone compared to wild-type mice
• while the hyperproliferative zone is reduced, the prehyperproliferative zone is increased
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• at E17.5, bones are severely shortened
• at birth, long bones in surviving mice are short and broad
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• at E14.5
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• at E17.5, mice exhibit 17.2% reduction of the half tibia length compared to wild-type mice
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• at birth, long bones in surviving mice are short and broad
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• cartilage differentiation is impaired
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• chondrocyte spreading is defective and adhesion to collagen and laminin is absent while adhesion to fibronectin is reduced 55% compared to in wild-type mice
• however, chondrocytes bind vitronectin normally
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• mice exhibit progressive reduction of chondrocyte proliferation (a 25% reduction at birth, 60% reduction at 3 weeks and no proliferation at 6 weeks) and increased apoptosis resulting in fewer chondrocytes than in wild-type mice
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• surviving mice fail to exhibit secondary ossification centers in the epiphysis
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• mineralization is delayed as evidenced by absent ossification centers in cervical vertebrae
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• in 50% of mice
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• at birth
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• mice that survive develop progressive dwarfism with a 40% reduction in skeletal length by 9 weeks of age
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• in 50% of mice
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• at birth
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• at E14.5
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• at E17.5, mice exhibit 17.2% reduction of the half tibia length compared to wild-type mice
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• in 50% of mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit progressive reduction of chondrocyte proliferation (a 25% reduction at birth, 60% reduction at 3 weeks and no proliferation at 6 weeks)
|
|
• most mice die shortly after birth due to respiratory distress
• however, 3 of 223 mice survive
|
|
• mice exhibit progressive reduction of chondrocyte proliferation (a 25% reduction at birth, 60% reduction at 3 weeks and no proliferation at 6 weeks)
|
|
• at E17.5, mice exhibit reductions of the half tibia length (17.2% reduction), the distance between the growth plate and the middle of diaphysis (43.2% reduction), the length of the bone marrow zone (45% reduction) and the length of the hypertrophic zone (15% reduction) compared to wild-type mice
• at E17.5, the resting zone is increased in length by 10% compared to wild-type mice
• however, the length of the proliferative zone and the total growth plate height are normal
• the growth plate is severely disorganized with large and round-shaped chondrocytes failing to glide over each other and form columns as in wild-type mice
• at 6 weeks of age, growth plates are completely disorganized and broadened
|
|
• at E17.5, mice exhibit 15% reduction in the length of the hypertrophic zone compared to wild-type mice
• while the hyperproliferative zone is reduced, the prehyperproliferative zone is increased
|
|
• at E17.5, bones are severely shortened
• at birth, long bones in surviving mice are short and broad
|
|
• at E14.5
|
|
• at E17.5, mice exhibit 17.2% reduction of the half tibia length compared to wild-type mice
|
|
• at birth, long bones in surviving mice are short and broad
|
|
• cartilage differentiation is impaired
|
|
• chondrocyte spreading is defective and adhesion to collagen and laminin is absent while adhesion to fibronectin is reduced 55% compared to in wild-type mice
• however, chondrocytes bind vitronectin normally
|
|
• mice exhibit progressive reduction of chondrocyte proliferation (a 25% reduction at birth, 60% reduction at 3 weeks and no proliferation at 6 weeks) and increased apoptosis resulting in fewer chondrocytes than in wild-type mice
|
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• surviving mice fail to exhibit secondary ossification centers in the epiphysis
|
|
• mineralization is delayed as evidenced by absent ossification centers in cervical vertebrae
|
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• in 50% of mice
|
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• at birth
|
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• mice that survive develop progressive dwarfism with a 40% reduction in skeletal length by 9 weeks of age
|
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• in 50% of mice
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• at birth
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• at E14.5
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• at E17.5, mice exhibit 17.2% reduction of the half tibia length compared to wild-type mice
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• in 50% of mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• while platelets exhibit activation at high shear stress, they form looser aggregates and disintegrate more frequently than wild-type platelets
• platelet aggregates display reduced annexinV positivity after perfusion unlike wild-type platelets
• platelet calcium response fluctuates and is lower than in wild-type platelets
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• while platelets exhibit activation at high shear stress, they form looser aggregates and disintegrate more frequently than wild-type platelets
• platelet aggregates display reduced annexinV positivity after perfusion unlike wild-type platelets
• platelet calcium response fluctuates and is lower than in wild-type platelets
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Hair and skin phenotypes of various keratinocyte conditional Itgb1 alleles
| N |
• mice are fertile unlike conditional null mice homozygous for Itgb1tm1Ref and hemizygous for Tg(KRT1-5-cre)5132Jlj
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• dermal fibrosis is accompanied by scattered melanin deposits
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• when cultured on a surface coated with collagen I and fibronectin, keratinocytes from 2.5 month old mice adhere but fail to spread and proliferate
• however, keratinocyte proliferation is similar to wild-type when cells are isolated from 6.5 month old mice
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• mildly affected
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• at P14, abnormally shaped hair follicles fail to grow as deeply into the subcutis compared to in control mice
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• loss of hair occurs between 6 and 12 months of age
• hair loss is delayed compared to conditional null mice homozygous for Itgb1tm1Ref and hemizygous for Tg(KRT1-5-cre)5132Jlj
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• coat is slightly thinner at 2 weeks of age compared to controls
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• at P14 about 60% of hair follicles are misshapen and arrested in morphogenesis
(J:148885)
• at P14 about 40% of hair follicles reach down to the muscle layer
(J:148885)
• at P14
(J:177979)
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• at P14 about 40% have severely abnormal and multilayered outer root sheaths
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• progressive hair loss is accompanied by development of dermal fibrosis with scattered melanin deposits
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• at P14 occasional small microblisters are seen at the dermal-epidermal junction
• however by 6.5 months of age almost no microblisters are seen in the epidermis of the back skin
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• dermal fibrosis is accompanied by scattered melanin deposits
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• when cultured on a surface coated with collagen I and fibronectin, keratinocytes from 2.5 month old mice adhere but fail to spread and proliferate
• however, keratinocyte proliferation is similar to wild-type when cells are isolated from 6.5 month old mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Hair and skin phenotypes of various keratinocyte conditional Itgb1 alleles
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• 70% of mice die by 6 weeks
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• mice develop an abnormal gait and walk with extended legs
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• ears become crumpled in appearance and are closely apposed to the head
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• ears become crumpled in appearance and are closely apposed to the head
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• the stratified epithelia of the esophagus displays abnormal basal cell morphology and reduced proliferation compared to in wild-type mice
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• by 7 weeks of age
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• ears become crumpled in appearance and are closely apposed to the head
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• ears become crumpled in appearance and are closely apposed to the head
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• after 4 weeks mice were 10 to 11 g compared to 20 g for wild-type mice
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• in a barrier function test, dye penetrate the superficial but not lower layers of the skin unlike in wild-type mice that demonstrate only occasional staining of the stratum corneum
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• mice develop skin inflammation with an increase in the number of macrophages around some but not all deformed hair follicles and giant cells found close to some hair bulbs
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• fibrosis is accompanied by large melanin deposits
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• at day 2, pigmentation on back skin at the midline and in several lines parallel to the ribs is reduced
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• ears become crumpled in appearance and are closely apposed to the head
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• ears become crumpled in appearance and are closely apposed to the head
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• by 7 weeks of age
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• in a barrier function test, dye penetrate the superficial but not lower layers of the skin unlike in wild-type mice that demonstrate only occasional staining of the stratum corneum
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• mice develop skin inflammation with an increase in the number of macrophages around some but not all deformed hair follicles and giant cells found close to some hair bulbs
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• at P14, abnormally shaped hair follicles fail to grow as deeply into the subcutis compared to in control mice
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• at 9 days a reduction in the number of hair follicles is apparent and by 4 weeks of age mice have few hairs left
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• loss of hair occurs between 2 and 5 weeks of age
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• short hairs are absent
(J:65038)
• beginning at day 9, hair follicles display abnormal morphologies such as shortened hair bulb and increased number of layers of outer root sheath cells, folding of layers of inner root sheath cells and amorphous, mislocated hair follicles
(J:65038)
• all hair follicles are severely distorted
(J:148885)
• at P14
(J:177979)
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• at 9 days a reduction in the number of hair follicles is apparent and by 4 weeks of age mice have few hairs left
(J:65038)
• no hair follicles are apparent at 7 weeks of age
(J:65038)
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• proliferation of hair follicles is decreased compared to in wild-type mice with proliferation of hair follicles reduced or absent at day 9 and 16, respectively
• however, there is no increase in apoptosis rates of hair follicles
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• mice develop dermal fibrosis
(J:65038)
• dermal fibrosis is detected by 5 weeks of age
(J:148885)
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• cell cycling in the basal layer is reduced compared to in wild-type mice
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• the basal keratinocyte layer is composed of several layers of roundish or polygonal cells unlike in wild-type mice
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• interfollicular epidermis consists of 2 to 7 layers of roundish, polygonal, or flattened keratinocytes that are often detached from the dermis forming large blisters
• at 5 weeks of age the epidermis of the back skin is severely hyperthickened but has fewer blisters compared to mice at 2 weeks of age
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• hyperthickened at 14 days of age
(J:177979)
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• the basement membrane at the dermal-epidermal junction is distorted compared to in wild-type mice
(J:65038)
• interfollicular epidermis consists of 2 to 7 layers of roundish, polygonal, or flattened keratinocytes that are often detached from the dermis forming large blisters
(J:148885)
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• mice develop small blisters on the tongue and esophagus at 6 weeks and blisters, bleeding and ulcerations in the anus region
(J:65038)
• interfollicular epidermis consists of 2 to 7 layers of roundish, polygonal, or flattened keratinocytes that are often detached from the dermis forming large blisters
(J:148885)
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• small skin wounds are apparent especially in areas of mechanical stress such as knees, elbows and ears
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• fibrosis is accompanied by large melanin deposits
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• defective adhesion and more pronounced spreading
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• cells do not grow into a confluent monolayer and undergo rapidly initiated terminal differentiation
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• patchy hair loss over the dorsal midline of the skull
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• intermixed with normal follicles
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• less affected than in Itgb1tm1Ref/Itgb1tm1Ref Tg(KRT1-5-cre)5132Jlj mice
• however, no subepidermal blistering is observed
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• defective adhesion and more pronounced spreading
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• cells do not grow into a confluent monolayer and undergo rapidly initiated terminal differentiation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal follicle morphogenesis and keratinocyte spreading and proliferation
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• patchy hair loss over the dorsal midline of the skull
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• less affected than in Itgb1tm1Ref/Itgb1tm1Ref Tg(KRT1-5-cre)5132Jlj mice
• however, no subepidermal blistering is observed
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• in a scratch wounding assay
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Hair and skin phenotypes of various keratinocyte conditional Itgb1 alleles
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• keratinocytes exhibit impaired adhesion to a collagen/fibronectin coated plastic dishes compared with control cells
(J:177979)
• keratinocytes do not adhere
(J:203018)
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• keratinocytes exhibit impaired adhesion to a collagen/fibronectin coated plastic dishes compared with control cells
(J:177979)
• keratinocytes do not adhere
(J:203018)
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• at P14, abnormally shaped hair follicles fail to grow as deeply into the subcutis compared to in control mice
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• at 14 days of age
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• at 2 weeks, hair coat development is impaired compared with control mice
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• hyperthickened with aberrant shaped cells at 14 days of age
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• at the epidermal-dermal junction at 14 days of age
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• at 5 weeks due to mechanical stress
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• at 2 weeks, skin pigmentation is impaired compared with control mice
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• at 2 weeks, skin pigmentation is impaired compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 90% of mutants die within 1 month of birth
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• starting a few days after birth mutants develop progressive defects in motor function including an inability to climb on inclined surfaces or cling to a round bar
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• starting a few days after birth mutants develop progressive muscle atrophy
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• starting a few days after birth mutants develop progressive muscle weakness
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• at E13.5 and E14.5 the subcutaneous nerves in mutants were thinner with an abnormal arborization pattern
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• at E13.5 few or no Schwann cell precursors are seen in the distal part of the developing subcutaneous or muscular innervations however by E16.5 Schwann cell numbers have returned to normal
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• mutants have decreased intramuscular innervation
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• neuromuscular junctions in the abdominal, soleus, and gastrocnemius muscles and the diaphragm appear immature in mutants at P21
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• at E10.5 transient abnormalities including decreased vagus nerve roots, fusion of nerves IX and X, or absence of nerve IX are seen however by E11.5 cranial nerve patterning has resembles that in controls
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• at P1 the sciatic nerve is abnormally thin and becomes progressively thinner by P21
• mutants nerves contain myelinated motor axons and large clusters of unsorted axons of varying diameters with few myelinated sensory axons
• at P21 some extracellular matrix free regions are seen in mutants
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• only a few myelinated sensory axons are seen at P21 in the sciatic nerve
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 7.7% of mice have an increase in the number of disseminated tumor cell emboli within lymphatic vessels near tumors
• however, no metastasis is detected in mice with tumors
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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