کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3213623 1203243 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Expression of exon-8-skipped kindlin-1 does not compensate for defects of Kindler syndrome
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Expression of exon-8-skipped kindlin-1 does not compensate for defects of Kindler syndrome
چکیده انگلیسی

BackgroundKindler syndrome (KS) is a rare, inherited skin disease characterized by blister formation and generalized poikiloderma. Mutations in KIND1, which encodes kindlin-1, are responsible for KS. c.1089del/1089+1del is a recurrent splice-site deletion mutation in KS patients.ObjectiveTo elucidate the effects of c.1089del/1089+1del at the mRNA and protein level.MethodsTwo KS patients with c.1089del/1089+1del were included in this study. Immunofluorescence analysis of KS skin samples using antibodies against the dermo-epidermal junction proteins was performed. Exon-trapping experiments were performed to isolate the mRNA sequences transcribed from genomic DNA harbouring c.1089del/1089+1del. β1 integrin activation in HeLa cells transfected with truncated KIND1 cDNA was analyzed.ResultsImmunofluorescence study showed positive expression of kindlin-1 in KS skin with c.1089del/1089+1del mutation. We identified the exon-8-skipped in-frame transcript as the main product among multiple splicing variants derived from that mutation. HeLa cells transfected with KIND1 cDNA without exon 8 showed impaired β1 integrin activation. Exon-8-coding amino acids are located in the FERM F2 domain, which is conserved among species, and the unstructured region between F2 and the pleckstrin homology domain.ConclusionThis study suggests that exon-8-skipped truncated kindlin-1 is functionally defective and does not compensate for the defects of KS, even though kindlin-1 expression in skin is positive.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Dermatological Science - Volume 61, Issue 1, January 2011, Pages 38–44
نویسندگان
, , , , , , , ,