Analysis Tools
mortality/aging
|
• homozygotes born naturally die within 1 day of birth
• all homozygotes obtained by cesarean at E18.5 die within 12.0-13.5 hrs whereas most wild-type and heterozygous controls die 15 hrs after isolation from the dam
|
growth/size/body
|
• body weight is normal at E18.5 after cesarean but significantly lower at P0
|
weight loss
(
J:261184
)
|
• homozygotes obtained by cesarean at E18.5 lose ~15% of their body weight within 12 hours versus ~5% in controls
|
integument
|
• at P0, keratinocytes in the lower layer of the stratum spinosum look like stratum basale keratinocytes, suggesting impaired differentiation
• upon in vitro differentiation, Mg2+ concentration is only minimally increased in keratinocytes
• keratinocyte differentiation-dependent induction of genes involved in skin barrier formation (Krt1, Lor, Flg, Elovl1 and Dgat2) is significantly impaired
|
|
• homozygotes exhibit significantly higher transepidermal water loss at E18.5 and P0 than wild-type and heterozygous controls
• at P0, homozygotes stain weakly by toluidine blue, indicating mild skin permeability barrier defects
|
|
• many vacuoles are observed in the corneocytes
|
|
• at P0, intercellular gaps are reduced indicating impaired lipid lamella formation; TEM analysis revealed that the lipid lamella is thinner
• at P0, acylceramide (omega-O-acylceramide) levels are reduced by ~50% whereas certain glucosylceramide species are increased in the epidermis
|
|
• at P0, the number of stratum corneum layers is increased to >20 relative to ~10 cell layers in wild-type controls
|
|
• at P0, heterochromatin structures are often observed in cell nuclei in the stratum granulosum
|
|
• at P0, lamellar bodies in stratum granulosum keratinocytes are small and undeveloped
|
|
• at P0, keratohyalin granules in the stratum granulosum are smaller but more numerous than in wild-type controls, suggestive of immature keratohyalin granules
|
|
• at P0, the stratum spinosum is thick
|
|
• skin is unusually unwrinkled at P0
|
shiny skin
(
J:261184
)
|
• skin is shiny at P0
|
homeostasis/metabolism
|
• homozygotes exhibit significantly higher transepidermal water loss at E18.5 and P0 than wild-type and heterozygous controls
• at P0, homozygotes stain weakly by toluidine blue, indicating mild skin permeability barrier defects
|
|
• in vitro differentiated keratinocytes exhibit a lower Mg2+ concentration than differentiated wild-type keratinocytes
• however, no difference in Mg2+ concentration is noted in the undifferentiated state
|
|
• at P0, acylceramide (omega-O-acylceramide) levels are reduced by ~50% in the epidermis
• esterified omega-hydroxyacyl-sphingosine (the major acylceramide class in mice), alpha-hydroxy fatty acyl-sphingosine, and non-hydroxy fatty acyl-dihydrosphingosine (a dihydroceramide) ceramides are decreased
• non-hydroxy fatty acyl-sphingosine ceramides with longer chains (C26:1 and C28:1) are decreased
|
|
• at P0, certain glucosylceramide species are increased in the epidermis
• non-hydroxy fatty acyl-sphingosine, omega-hydroxyacyl-sphingosine, and non-hydroxy fatty acyl-phytosphingosine (a phytoceramide) ceramides are increased
• non-hydroxy fatty acyl-sphingosine ceramides with shorter chain lengths (C16-C24) are increased
|
|
• at P0, all esterified omega-hydroxyacyl-sphingosine species are decreased in the epidermis, irrespective of the chain lengths
|
|
• at P0, all omega-hydroxyacyl-sphingosine species are increased in the epidermis
|
cellular
|
• at P0, keratinocytes in the lower layer of the stratum spinosum look like stratum basale keratinocytes, suggesting impaired differentiation
• upon in vitro differentiation, Mg2+ concentration is only minimally increased in keratinocytes
• keratinocyte differentiation-dependent induction of genes involved in skin barrier formation (Krt1, Lor, Flg, Elovl1 and Dgat2) is significantly impaired
|
