Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-9-19
pubmed:abstractText
Harlequin Ichthyosis (HI) is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-10431236, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-10431237, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-10431238, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-10612259, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-10951284, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-10998161, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-11060357, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-11279093, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-11483617, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-11564887, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-11679007, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-11710923, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-11741264, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-11927667, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-12763760, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-1281866, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-12915478, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-13428781, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-1353738, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-15158913, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-15280376, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-15537638, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-15756637, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-1594045, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-15951745, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-15996518, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-16007253, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-16675967, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-16798073, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-16847209, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-1688598, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-16902423, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-17095732, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-17353664, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-17591952, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-17611579, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-17927575, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-18245815, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-184464, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-1940639, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-1991982, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-2478600, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-2579164, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-3790600, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-426527, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-8097623, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-8415297, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-8507075, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-8969186, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-9406821, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-9502735, http://linkedlifedata.com/resource/pubmed/commentcorrection/18802465-9517915
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1553-7404
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e1000192
pubmed:dateRevised
2011-6-21
pubmed:meshHeading
More...