Phenotypes Associated with This Genotype

Genotype
MGI:2683729

• Allelic Composition: St14^tm1Bug/St14^tm1Bug
• Genetic Background: involves: 129P2/OlaHsd

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

homeostasis/metabolism

impaired skin barrier function ( J:86715 )

• defects in stratum corneum (SC) formation result in total loss of epidermal barrier function

• epidermal defects are associated with selective loss of both proteolytically processed filaggrin monomer units and the NH2-terminal filaggrin S-100 regulatory protein, with severe accumulation of profilaggrin and aberrant profilaggrin-processing products in the SC

• epidermal deficiency is not corrected with time or by systemic expression of Matriptase/MT-SP1

• prolonged exposure of neonatal mutant transplanted skin to dehydration (air) leads to severe compensatory hyperproliferative ichthyosis

integument

abnormal keratinocyte differentiation ( J:86715 )

• newborn homozygotes exhibit defective proteolytic processing of profilaggrin and incorporation of aberrantly processed profilaggrin into the SC during terminal corneocyte differentiation

impaired skin barrier function ( J:86715 )

• defects in stratum corneum (SC) formation result in total loss of epidermal barrier function

• epidermal defects are associated with selective loss of both proteolytically processed filaggrin monomer units and the NH2-terminal filaggrin S-100 regulatory protein, with severe accumulation of profilaggrin and aberrant profilaggrin-processing products in the SC

• epidermal deficiency is not corrected with time or by systemic expression of Matriptase/MT-SP1

• prolonged exposure of neonatal mutant transplanted skin to dehydration (air) leads to severe compensatory hyperproliferative ichthyosis

alopecia ( J:86715 )

• at 3 wks after transplantation onto nude mice, neonatal mutant skin displays absence of erupted pelage hairs; only a few pelage hair shafts are found as thin, broken fibers surrounded by dense sheaths of cornified debris

abnormal epidermis stratum corneum morphology ( J:86715 )

• newborn homozygotes display numerous defects in stratum corneum (SC) formation

enlarged corneocyte envelope ( J:86715 )

• mutant corneocyte envelopes (CEs) isolated from newborn homozygotes are enlarged by 15% relative to wild-type CEs

• however, the shape, surface morphology, and mechanical integrity of mutant CEs remain unaffected

abnormal stratum corneum lipid matrix formation ( J:86715 )

• newborn homozygotes exhibit lipid matrix defects, as shown by a ~50% reduction in free fatty acids, a ~25% increase in cholesterol, and a nearly 10-fold decrease in sterol esters in total epidermis and SC, along with a >2-fold increase in phospholipid content in the SC relative to control littermates

• mutant intercorneocyte lipids appear poorly organized with short and misaligned lipid lamellae

hyperkeratosis ( J:86715 )

• at 3 wks after transplantation onto nude mice, neonatal mutant skin displays severe hyperkeratosis, associated with hyperproliferation of basal keratinocytes and keratin-6 overexpression

impaired stratum corneum desquamation ( J:86715 )

• unlike wild-type controls, where the SC is completely removed exposing the lower epidermal layers after 12 successive rounds of tape stripping, newborn homozygotes display only minimal SC removal with a significant reduction in SC protein loss after tape stripping, indicating increased mechanical resistance

abnormal epidermis stratum granulosum morphology ( J:86715 )

• newborn homozygotes display rare and poorly formed lamellar bodies with wavy, short, and disorganized lipid structures in the granular layer of the epidermis

acanthosis ( J:86715 )

• at 3 wks after transplantation onto nude mice, neonatal mutant skin displays profound acanthosis

thick epidermis ( J:86715 )

• at 3 wks after transplantation onto nude mice, neonatal mutant skin displays grotesque epidermal thickening

scaly skin ( J:86715 )

• at 3 wks after transplantation onto nude mice, neonatal mutant skin displays large plate-like epidermal scales

cellular

abnormal keratinocyte differentiation ( J:86715 )

• newborn homozygotes exhibit defective proteolytic processing of profilaggrin and incorporation of aberrantly processed profilaggrin into the SC during terminal corneocyte differentiation