Mouse Genome Informatics
hm
    Plectm1Gwi/Plectm1Gwi
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygotes die between day 1 and 3 after birth

cardiovascular system
• 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
• ultrastructurally, mutant cardiomyocytes show partial disintegration of intercalated discs and adjacent myofibers
• large blisters are often accompanied by bleedings, particularly at the extremities, suggesting disruption of vascular endothelial cells

growth/size/body
• postnatally, most homozygotes are smaller than wild-type littermates, as a result of reduced gain in body weight

muscle
• 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
• ultrastructurally, mutant cardiomyocytes show partial disintegration of intercalated discs and adjacent myofibers
• 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
• 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
• mutants show abnormalities that resemble minicore myopathies in skeletal muscle and disintegration of intercalated discs in heart

integument
• the mutant skin is detached at the fore- and hindlimbs and sometimes around the mouth and nasal cavities
• 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
• 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
• the basal cell layer is completely absent from the upper epidermal layers that form the blister roof
• 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
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Epidermolysis Bullosa Simplex with Muscular Dystrophy 226670 J:59000
Epidermolysis Bullosa Simplex, Ogna Type 131950 J:59000