کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2177897 1094692 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dose-Dependent Interaction of Tbx1 and Crkl and Locally Aberrant RA Signaling in a Model of del22q11 Syndrome
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Dose-Dependent Interaction of Tbx1 and Crkl and Locally Aberrant RA Signaling in a Model of del22q11 Syndrome
چکیده انگلیسی

Summary22q11 deletion (del22q11) syndrome is characterized genetically by heterozygous deletions within chromosome 22q11 and clinically by a constellation of congenital malformations of the aortic arch, heart, thymus, and parathyroid glands described as DiGeorge syndrome (DGS). Here, we report that compound heterozygosity of mouse homologs of two 22q11 genes, CRKL and TBX1, results in a striking increase in the penetrance and expressivity of a DGS-like phenotype compared to heterozygosity at either locus. Furthermore, we show that these two genes have critical dose-dependent functions in pharyngeal segmentation, patterning of the pharyngeal apparatus along the anteroposterior axis, and local regulation of retinoic acid (RA) metabolism and signaling. We can partially rescue one salient feature of DGS in Crkl+/−;Tbx1+/− embryos by genetically reducing the amount of RA produced in the embryo. Thus, we suggest that del22q11 is a contiguous gene syndrome involving dose-sensitive interaction of CRKL and TBX1 and locally aberrant RA signaling.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 10, Issue 1, January 2006, Pages 81–92
نویسندگان
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