کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2119478 1085394 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A transgenic, mesodermal specific, Dkk1 mouse model recapitulates a spectrum of human congenital limb reduction defects
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
A transgenic, mesodermal specific, Dkk1 mouse model recapitulates a spectrum of human congenital limb reduction defects
چکیده انگلیسی

SummaryCongenital limb reduction defects occurring in isolation of other developmental abnormalities continue to be an important medical problem in which little progress has been made. Herein we generated transgenic mice expressing Dkk1 in an appendicular mesodermal pattern. Prx1-Dkk1 mice recapitulate a full spectrum of human congenital limb reduction defects, without other developmental issues, and have normal life-spans. Importantly, a close examination of the inheritance pattern suggests that there is a significant degree of incomplete penetrance as progeny of phenotypically positive or phenotypically negative, but genotypically positive Prx1-Dkk1 mice, consistently give rise to both phenotypically positive mice and phenotypically normal-appearing mice. Thus, this heterogeneous phenotype is reproducible with each generation regardless of the phenotype of the parents. We further go on to identify that mesenchymal stem cells from Prx1-Dkk1 mice have limited proliferative ability, but normal differentiation potential, which may explain the mechanism for the limb reduction defects observed. We believe Prx1-Dkk1 mice may prove useful in the future to study the mechanisms underlying the development of congenital limb reduction defects.


► Prx1-Dkk1 mice recapitulate a spectrum of human congenital limb reduction defects.
► MSCs from Prx1-Dkk1 mice show a proclivity to apoptosis both in vivo and in vitro.
► Wnt/β-catenin inhibition in Prx1-Dkk1 tissues correlate with phenotype severity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Differentiation - Volume 83, Issue 4, April 2012, Pages 220–230
نویسندگان
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