Harlequin ichthyosis model mouse reveals alveolar collapse and severe fetal skin barrier defects.

[harlequin ichthyosis]

Harlequin ichthyosis (HI ), which is the most severe genodermatosis , is caused by loss -of-function mutations in ABCA 12 , a member of the ATP-binding cassette transporter family . To investigate the pathomechanism of HI and the function of the ABCA 12 protein , we generated ABCA 12 -deficient mice (Abca 12 (-/-)) by targeting Abca 12 . Abca 12 (-/-) mice closely reproduce the human HI phenotype , showing marked hyperkeratosis with eclabium and skin fissure . Lamellar granule abnormalities and defective ceramide distribution were remarkable in the epidermis . Skin permeability assay of Abca 12 (-/-) fetuses revealed severe skin barrier dysfunction after the initiation of keratinization . Surprisingly , the Abca 12 (-/-) mice also demonstrated lung alveolar collapse immediately after birth . Lamellar bodies in alveolar type II cells of the Abca 12 (-/-) mice lacked normal lamellar structures . The level of surfactant protein B , an essential component of alveolar surfactant , was reduced in the Abca 12 (-/-) mice . Fetal therapeutic trials with systemic administration of retinoid or dexamethasone , which are effective for HI and respiratory distress , respectively , to the pregnant mother mice neither improved the skin phenotype nor extended the survival period . Our HI model mice reproduce the human HI skin phenotype soon after the initiation of fetal skin keratinization and provide evidence that ABCA 12 plays pivotal roles in lung and skin barrier functions .

Diseases
Validation

Diseases presenting "respectively" symptom

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

alpha-thalassemia

benign recurrent intrahepatic cholestasis

carcinoma of the gallbladder

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cushing syndrome

cystinuria

dedifferentiated liposarcoma

dentin dysplasia

dentinogenesis imperfecta

epidermolysis bullosa simplex

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

harlequin ichthyosis

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

kallmann syndrome

lamellar ichthyosis

liposarcoma

neonatal adrenoleukodystrophy

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyruvate dehydrogenase deficiency

scrub typhus

triple a syndrome

von hippel-lindau disease

well-differentiated liposarcoma

wolf-hirschhorn syndrome

You can validate or delete this automatically detected symptom