Analysis Tools
mortality/aging
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• homozygotes die between day 1 and 3 after birth
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cardiovascular system
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• light microscopy reveals no overt anomalies in the myocardium, atrial and ventricular walls; no necrotic cardiomyocytes are observed
• however, in affected cells, sarcomeres appear loosely and irregularly arranged relative to wild-type
• in addition, aberrant isolated myofibril bundles and accumulation of Z-band material are observed
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• ultrastructurally, mutant cardiomyocytes show partial disintegration of intercalated discs and adjacent myofibers
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hemorrhage
(
J:59000
)
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• large blisters are often accompanied by bleedings, particularly at the extremities, suggesting disruption of vascular endothelial cells
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growth/size/body
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• postnatally, most homozygotes are smaller than wild-type littermates, as a result of reduced gain in body weight
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muscle
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• light microscopy reveals no overt anomalies in the myocardium, atrial and ventricular walls; no necrotic cardiomyocytes are observed
• however, in affected cells, sarcomeres appear loosely and irregularly arranged relative to wild-type
• in addition, aberrant isolated myofibril bundles and accumulation of Z-band material are observed
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• ultrastructurally, mutant cardiomyocytes show partial disintegration of intercalated discs and adjacent myofibers
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• although all muscle groups show pathological changes, the paravertebral and distal limb muscles are preferentially affected
• focal disruptions of sarcomeres affecting Z-lines and adjacent myofibrils are frequently observed
• in affected areas, mutant Z-lines appear loose, with a poorly focused, smearing and streaming appearance
• overall, the sarcolemma remains structurally intact, except for occasional short ruptures of the plasma membrane
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• degenerating, necrotic changes of various degrees are found in 0.5%-1% of single mutant muscle fibers versus less than 0.1% found in wild-type
• myophagocytosis is occasionally observed in association with necrotic fibers
• necrotic changes involving focal loss of myofilaments of various degrees are noted in ~20% of muscle fibers; no apoptotic events are observed in the nuclei of muscle cells
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• mutants show abnormalities that resemble minicore myopathies in skeletal muscle and disintegration of intercalated discs in heart
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integument
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• parts of the basal lamina overlying the dermis are covered by a partially fragmented cell membrane, possibly a remnant of the basal cell surface membrane of keratinocytes
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• disruption and degeneration of the basal epidermal cell layer is observed at the blister margins
• the number of mutant hemidesmosomes is reduced to ~50% of wild-type mice; their mechanical stability is altered
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• the basal cell layer is completely absent from the upper epidermal layers that form the blister roof
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• basal keratinocyte disruption occurs throughout the cytoplasm, in some instances in perinuclear regions, in others through basal or apical cytoplasmic regions
• other basal keratinocytes show granular dissolution of cytoplasmic components in spite of preservation of some mitochondria and dense bodies; in these cells, keratin filaments are not detectable
• at the center of blisters, basal keratinocytes are no longer detectable and replaced by a fluid-filled space
• mutant keratin filaments appear looser and less bundled than wild-type, esp. at their insertion site into the inner plate structure
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blistering
(
J:59000
)
|
• homozygotes exhibit large blisters (up to 1 cm in diameter) at the upper and lower extremities, often accompanied by bleeding
• in skin, large blisters are located between the dermis and the superficial epidermal layers
• smaller blisters are present at other sites of the integumentum esp. in the epithelial layers of the oral mucosa and the tongue
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• the mutant skin is detached at the fore- and hindlimbs and sometimes around the mouth and nasal cavities
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| epidermolysis bullosa simplex Ogna type | DOID:0060736 |
OMIM:131950 |
J:59000 | |
| epidermolysis bullosa simplex with muscular dystrophy | DOID:0090017 |
OMIM:226670 |
J:59000 | |
