Analysis Tools
mortality/aging
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• mice are born at the expected Mendelian ratio but die within 20 hours of birth
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vision/eye
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• lack of eyelids is readily apparent at E16.5
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• eyes are already opened at birth, secondary to failure of eyelid formation
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growth/size/body
weight loss
(
J:335426
)
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• mice lose up to 15% of their initial body weight within 9 hours after birth
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integument
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• impaired keratinocyte differentiation is associated with a defect in the transition from proliferating to differentiating keratinocytes together with an increase in basal cell proliferation
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• newborns exhibit an increase in proliferating basal Ki67+ Krt14+ cells
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• newborns exhibit impaired skin permeability barrier function that results in water loss, as determined by an outside-in toluidine blue exclusion assay and an inside-out tight junction barrier assay
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• newborns exhibit a more densely packed (compacted) stratum corneum due to a reduced lipid content
• filaggrin granules are nearly absent in the stratum corneum
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• filaggrin protein and mRNA levels are significantly reduced whereas involucrin is up-regulated both at protein and mRNA levels; loricrin levels remain unchanged despite a reduction observed in L-granule size
• ceramides and glucosylceramides (GlcCer) are completely absent in the stratum corneum
• both polar and nonpolar lipids are significantly reduced in the stratum corneum, with a more prominent reduction noted in nonpolar lipids (ceramides)
• lipids exhibit a dot-like distribution, unlike the weave-like distribution seen in wild-type controls
• in vitro, primary keratinocytes isolated from P0.5 show a reduction in nonpolar lipids after 3 days of differentiation
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• filaggrin granule distribution appears marginated in the cytoplasm, forming a circular edge in the cells of the stratum granulosum
• filaggrin granules are smaller and appear elongated
• filaggrin granules are arranged around the nucleus, and not linearly distributed along the stratum granulosum, as seen in wild-type epidermis
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• interface between the granular layer and the stratum corneum is almost devoid of lamellar bodies, as indicated by weak staining of cathepsin D; both the proenzyme and the enzymatically active forms are markedly reduced in the epidermis
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• TEM analysis shows that both keratohyalin granules containing pro-filaggrin and loricrin-containing L-granules are smaller than in control mice
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• newborns show reduced epidermal thickness
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• newborns exhibit shiny, wrinkled, and sticky skin
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shiny skin
(
J:335426
)
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• newborn skin shows simultaneous expression of Krt14 and Krt10 in several cells, suggesting that the keratin switch is delayed/impaired at an early differentiation stage, as confirmed by an increase in Krt14 mRNA expression
• deregulation of epidermal differentiation is already observed at E17.5 in both dorsal and ventral skin
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homeostasis/metabolism
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• mRNA expression of transglutaminase enzymes is significantly reduced (Tgm5) or shows a tendency to decrease (Tgm1 and Tgm3)
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dehydration
(
J:335426
)
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• neonatal loss of weight is due to dehydration
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• newborns exhibit impaired skin permeability barrier function that results in water loss, as determined by an outside-in toluidine blue exclusion assay and an inside-out tight junction barrier assay
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• neonatal epidermis shows a significant reduction in the levels of cholesterol esters (C16-18)
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• neonatal epidermis shows marked accumulation of several phosphatidylserine species including ether bonds
• only a few phosphatidylinositol species are reduced in the epidermis
• phosphatidylethanolamines remain relatively unchanged
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• lipidomic analysis of neonatal epidermis shows a significant decrease in sphingomyelins, due to the reduction in several ceramide species
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• lipidomic analysis of neonatal epidermis by UPLC-MS/MS shows that the number of ceramide species involved in skin barrier permeability is severely deregulated
• ceramides with long chain fatty acids (C>22) are significantly reduced, whereas ceramide species with short-chain aftty acids (C16-22) are increased
• specifically, saturated ceramides (d18:0/16:0), (d18:1/16:0), (d18:0/24:0) and (d18:0/26:0) show significant accumulation, whereas monounsaturated ceramides with C24-26, such as (d18:1/24:0), (d18:1/25:0), (d18:1/26:0) and (d18:1/26:1) are significantly reduced
• altered ceramide profile is likely a result of a reduction in mRNA levels of key enzymes involved in ceramide biosynthesis including Sptlc1, Kdsr, Degs1, Degs2, Smpd1-3, Elovl6, and Elovl7
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• neonatal epidermis shows a significant reduction in triacylglycerol (TAG) levels; this is associated with a significant increase of several 1,2-diacyglycerol species in the epidermis
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cellular
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• impaired keratinocyte differentiation is associated with a defect in the transition from proliferating to differentiating keratinocytes together with an increase in basal cell proliferation
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• newborns exhibit an increase in proliferating basal Ki67+ Krt14+ cells
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behavior/neurological
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• newborn pups lack milk in their stomachs, suggesting maternal neglect
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