Phenotypes Associated with This Genotype

Genotype
MGI:3513191

• Allelic Composition: Plec^tm1Gwi/Plec^tm1Gwi
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

postnatal lethality, complete penetrance ( J:59000 )

• homozygotes die between day 1 and 3 after birth

cardiovascular system

abnormal myocardial fiber morphology ( J:59000 )

• 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

abnormal intercalated disk morphology ( J:59000 )

• ultrastructurally, mutant cardiomyocytes show partial disintegration of intercalated discs and adjacent myofibers

hemorrhage ( J:59000 )

• large blisters are often accompanied by bleedings, particularly at the extremities, suggesting disruption of vascular endothelial cells

growth/size/body

decreased body weight ( J:59000 )

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

muscle

abnormal myocardial fiber morphology ( J:59000 )

• 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

abnormal intercalated disk morphology ( J:59000 )

• ultrastructurally, mutant cardiomyocytes show partial disintegration of intercalated discs and adjacent myofibers

abnormal skeletal muscle fiber morphology ( J:59000 )

• 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

muscle degeneration ( J:59000 )

• 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

myopathy ( J:59000 )

• mutants show abnormalities that resemble minicore myopathies in skeletal muscle and disintegration of intercalated discs in heart

integument

abnormal dermal layer morphology ( J:59000 )

• 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

abnormal epidermis stratum basale morphology ( J:59000 )

• 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

absent epidermis stratum basale ( J:59000 )

• the basal cell layer is completely absent from the upper epidermal layers that form the blister roof

abnormal keratinocyte morphology ( J:59000 )

• 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

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

skin detachment ( J:59000 )

• the mutant skin is detached at the fore- and hindlimbs and sometimes around the mouth and nasal cavities

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