Analysis Tools
mortality/aging
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• mice are born at the expected Mendelian ratio but die within the first day of birth, with an average lifetime of ~12 hours
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growth/size/body
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• mice exhibit significantly reduced birth weight relative to wild-type controls
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weight loss
(
J:233599
)
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• newborn mice lose significantly more weight than wild-type controls during a period of 7 hours
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integument
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• subcutaneous adipocyte layer thickness is reduced, as shown by Trichrome III blue staining of back skin
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• newborn mice show a 3-fold increase in transepidermal water loss in non-lesional areas relative to wild-type controls
• several tight junction components display altered localization with either a discontinuous (zonula occludens 1) or diffuse (occludin) distribution; claudin-1 expression extends into the basal region
• the tight junction barrier (i.e. inside-out liquid barrier) is disrupted in the epidermis, as shown by a biotin penetration assay
• in contrast, the outside-in barrier remains intact in non-lesional areas, as shown by a toluidine blue penetration assay; blue staining is noted only at skin lesions
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• newborn mice lack whiskers
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• the stratum corneum is often loose and flaky, with reduced cohesion between corneocyte layers, and is reduced in paw skin
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• corneocytes appear somewhat smaller
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• cell separation is initiated in the granular layer
• complete detachment typically occurs between the granular and the spinous layers
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• the granular layer is markedly reduced in thickness in paw skin
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• widening of intercellular spaces is observed mostly in the suprabasal layers
• desmosomes are sparse and smaller, despite up-regulation of most desmosomal proteins including PKP3
• desmosomes show a ~90% reduction in number, a ~45% reduction in size, and lack the inner plaque structure; however, keratin filaments remain anchored at the residual desmosomes
• epidermal adhesion in the basal layer and adhesion to the underlying basement membrane appear normal
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• isolated keratinocytes exhibit strongly reduced intercellular cohesion and delayed tight junction formation
• in response to mild mechanical stress (rotation), epithelial sheets of keratinocyte monolayers quickly disintegrate into small fragments, whereas wild-type epithelial sheets remain intact
• at 24 hrs after calcium addition, occludin is significantly reduced, while membrane recruitment of all tight junction proteins is delayed and remains irregular and partially discontinuous
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skin lesions
(
J:233599
)
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• newborn mice soon develop skin lesions in the absence of obvious mechanical trauma
• however, no skin blistering is observed
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• neonatal paw skin is slightly thinner than normal
• however, dorsal skin thickness is normal with no detectable changes in proliferation
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• total expression of all keratins tested is increased, indicating keratin activation
• keratin 17, normally expressed upon keratinocyte activation and inflammation, is increased in the epidermis basal and the suprabasal layers
• after Ca2+ switch, isolated keratinocytes exhibit reduced transepithelial electrical resistance relative to wild-type keratinocytes
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• isolated keratinocytes exhibit reduced reduced proliferation rates relative to wild-type keratinocytes
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• newborn mice exhibit fragile skin with lesions
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homeostasis/metabolism
dehydration
(
J:233599
)
|
• newborn mice exhibit a defect in the tight junction barrier leading to dehydration
|
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• newborn mice show a 3-fold increase in transepidermal water loss in non-lesional areas relative to wild-type controls
• several tight junction components display altered localization with either a discontinuous (zonula occludens 1) or diffuse (occludin) distribution; claudin-1 expression extends into the basal region
• the tight junction barrier (i.e. inside-out liquid barrier) is disrupted in the epidermis, as shown by a biotin penetration assay
• in contrast, the outside-in barrier remains intact in non-lesional areas, as shown by a toluidine blue penetration assay; blue staining is noted only at skin lesions
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adipose tissue
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• subcutaneous adipocyte layer thickness is reduced, as shown by Trichrome III blue staining of back skin
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cellular
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• newborn mice exhibit defects in desmosome formation and loss of intercellular adhesion in the suprabasal layers of the skin
• several tight junction components display altered localization with either a discontinuous (zonula occludens 1) or diffuse (occludin) distribution; claudin-1 expression extends into the basal region
• isolated keratinocytes exhibit strongly reduced intercellular cohesion and delayed tight junction formation
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• isolated keratinocytes exhibit reduced reduced proliferation rates relative to wild-type keratinocytes
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