Croatia - Linder - Cornification Flashcards
What are the three key lipids present in the lipid envelope?
ceramides, cholesterol, fatty acids
A mutation in the NSDHL gene results in what clinical disease? Why?
X-linked Cornification disorder, Blaschko’s lines; gene encodes for 3 beta-hydroxysteroid dehydrogenase and mutation interrupts cholesterol synthesis and leads to toxic metabolites
What are some of the filaggrin degradation products?
histidine, pyrrolidone-5-carboxylic acid, urocanic acid
What is the function of corneodesmosin?
stabilizes desmosomes and increases their flexibility & elasticity through glycine-loop properties
What changes in the conditions occur from the lower stratum corneum to the upper SC to allow desquamation to occur (pH, water content, Ca2+ content)?
neutral pH –> acidic pH; High H20 –> low H20; high Ca2+ –> low Ca2+; formation of natural moisturizing factors in upper SC
A mutation in what gene causes an autosomal recessive ichthyosis in Norfolk terriers?
KRT10 (keratin 10)
What does the Nile red stain highlight?
lipids
What are the clinical features of American Bulldog ichthyosis?
ventral erythema, brown/tan scale, wrinkled skin, yeast overgrowth, otitis, intertrigo, pododermatitis, pruritus
T/F: There are no cell junction related ichthyoses reported in animals.
True– though several reported in people
Palmoplantar keratoderma in Dogues de Bordeaux is caused by a mutation in what gene?
KRT16 (keratin 16)
Mutations in genes that encode for what structures result in epidermolytic ichthyosis?
keratins
A mutation in the ASPRV1 gene affects what protein and results in what clinical disease?
retroviral-like aspartic protease 1 (AKA SASPase); GSD ichthyosis
What are the main proteins found in tight junctions?
claudins
What does a mutation in the ST14 gene affect (protein and function)?
matriptase (serine protease); affects filaggrin processing and corneodesmosome breakdown
What creates the stratum disjunctum seen on histopathology?
breakdown of corneodesmosomes
A mutation in the gene that codes for fatty acid transport protein 4 (FATP4) results in what disease?
Great Dane ichthyosis
What are the clinical features of the KCS/Ichthyosiform Dermatosis of CKCS?
KCS, curly coat, erosions, sloughing claws and hyperkeratosis
A mutation in the ST14 gene affects what protein and results in what clinical disease?
matriptase (serine protease); Akhal-Teke horse naked foal syndrome
Tight junctions are cell-cell junctions that seal the periphery of keratinocytes together in what layer of the epidermis?
stratum granulosum
What does patatin-like phospholipase-1 (PNPLA-1) code for? What disease results from its mutation?
acylceramide, which has a role in glycerophospholpid metabolism & cutaneous barrier function; mutation results in Golden Retriever ichthyosis
What are clinical features of the epidermolytic hyperkeratosis of Norfolk terriers?
mild, hyperpigmented scaling; skin fragility, non-erythematous
What factors help to lower the pH during desquamation of the SC?
sodium/hydrogen antiporter; breakdown of phospholipids into free fatty acids; breakdown of filaggrin to amino acids/histidine/NMF; exogenous substances (sebum, microflora)
What are the components of ceramides?
fatty acids + sphingoid bases
Ichthyosis fetalis in Chianina cattle is due to a mutation in what gene? To what disease is this similar in people?
ABCA12, harlequin ichthyosis
Most autosomal recessive congenital ichthyoses result from a disorder of the formation of what?
cornified lipid envelope
What protein is reponsible for compaction of keratin intermediate filament network in the process of cornification?
filaggrin
How does the mutation in lamellar ichthyosis of Jack Russell Terriers affect corneocyte stability?
lack transglutaminase-1 activity => no cross-linking of the cornified envelope => corneocyte fragility
What are the two key components of successful treatment of nuclear interaction partner of ALK-like domain containing 4 (NIPAL4) mutant affected dogs?
1) Block altered lipid pathway and cytotoxicity, 2) Replace altered/deficient lipids
What does nuclear interaction partner of ALK-like domain containing 4 (NIPAL4) code for? What disease results from its mutation?
ichthyin; American bulldog ichthyosis
What are the clinical features of ichthyosis fetalis?
still-born or death within a few days; microtia and eversion of the skin of the lips & eyelids
_____ is an essential fatty acid in the diet that is required for cornified lipid envelope formation and function.
linoleic acid
What are the clinical features of the lamellar ichthyosis of Jack Russell Terriers?
severe phenotype; large, paper-like, tan-white scale; often entire body, including ear canals; secondary yeast/bacterial infections; require significant supportive care
A mutation in what gene causes an autosomal recessive ichthyosis in Jack Russell terriers?
TGM1 gene (transglutaminase-1)
What is the function of ABCA12 gene?
encodes for an ATP-binding cassette transporter that has a major role in transportation of lipids in the epidermis responsible for cholesterol efflux from keratinocytes
What is the function of tight junctions?
forms a barrier to electrolyte and solute movements in the upper epidermis (helps to limit transepidermal water loss)
Great Dane ichthyosis results from a mutation in what gene?
SLC27A4 that affects the fatty acid transprot protein 4 (FATP4)
What are the histologic features of hereditary nasal parakeratosis?
parakeratotic hyperkeratosis, serum lakes, keratinocyte vacuolation, epidermal hyperplasia, mild inflammation
Hereditary nasal parakeratosis in Labs is attributed to a mutation in what gene?
SUV39H2
T/F: With the nuclear interaction partner of ALK-like domain containing 4 (NIPAL4) mutation, the cornified lipid envelope is absent.
True & lipid envelop is abnormally structured, the cornified envelop is thinner, reduced lamellar bodies
What are some of the proteins in the cornified envelope?
envoplakin, periplakin, loricrin, involucrin, filaggrin
What is the function of the cornified lipid envelope?
seals the lipid envelope to the corneocyte surface
What are the clinical features of Great Dane ichthyosis?
marked skin wrinkles (head, legs), severe fine white-yellow scaling, greasy skin surface, axillary and inguinal areas dry and leathery; other developmental defects - hydronephrosis, interstitial pneumonia, auditory canal abnormalities
What does the NSDHL gene encode for?
3 beta-hydroxysteroid dehydrogenase, involved in cholesterol metabolism
What does a mutation in the ASPRV1 gene affect (protein and function)?
retroviral-like aspartic protease 1 (AKA SASPase); affects processing of profilaggrin to filaggrin
A mutation in what gene causes lethal acrodermatitis of Bull Terriers?
MKLN1 (muskelin-1)
What keratins are present in the stratum granulosum?
KRT1, KRT2, KRT10
Mutation in the ABCA12 gene results in what disease? In what specie(s)?
Ichthyosis fetalis (harlequin ichthyosis), cattle, humans
What is the function of transglutaminases in the cornified envelope?
cross-link keratin intermediate filaments, cornified envelope proteins and adhesion complexes
A mutation in what gene causes an autosomal recessive, congenital keratoconjunctivitis sicca and ichthyosiform dermatitis in Cavalier King Charles Spaniels?
FAM83H
What is the function of ichthyin?
magnesium transporter for fatty acid transport protein; alters FFA coenzyme esterification
What is present in corneocytes below the plasma membrane that stabilizes the cell periphery?
Cornified envelope
What is the mutation in American Bulldog ichthyosis?
nuclear interaction partner of ALK-like domain containing 4 (NIPAL4)
Mutations in genes that encode for what structure(s) result in non-epidermolytic ichthyosis?
lipids, non-keratin proteins, desquamation
How are essential fatty acids and cholesterol delivered to the corneocyte?
transport pumps
What is the mutation in Golden retriever ichthyosis?
patatin-like phospholipase-1 (PNPLA-1)
What protein adheres the corneodesmosome to the cornified envelope? Where does the protein come from?
corneodesmosin; lamellar bodies
What are lamellar bodies and what is their function?
secretory vesicles that deliver stacks of lipids and proteins (enzymes, inhibitors) to the external surface of the developing corneocyte –> forms the lipid envelope
