Open AccessViable Mice with Compound Mutations in the Wnt/Dvl Pathway Antagonists nkd1 and nkd2
Author(s) -
Zhang Shu,
Tolga Çağatay,
Manami Amanai,
Mei Zhang,
Janine Kline,
Diego H. Castrillón,
Raheela Ashfaq,
Orhan K. Öz,
Keith A. Wharton
Publication year - 2007
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00133-07
Subject(s) - wnt signaling pathway , biology , axin2 , microbiology and biotechnology , beta catenin , signal transduction
Gradients of Wnt/β-catenin signaling coordinate development and physiological homeostasis in metazoan animals. Proper embryonic development of the fruit flyDrosophila melanogaster requires the Naked cuticle (Nkd) protein to attenuate a gradient of Wnt/β-catenin signaling across each segmental anlage. Nkd inhibits Wnt signaling by binding the intracellular protein Dishevelled (Dsh). Mice and humans have twonkd homologs,nkd1 andnkd2 , whose encoded proteins can bind Dsh homologs (the Dvl proteins) and inhibit Wnt signaling. To determine whethernkd genes are necessary for murine development, we replacednkd exons that encode Dvl-binding sequences withIRES -lacZ /neomycin cassettes. Mutants homozygous for eachnkd lacZ allele are viable with slightly reduced mean litter sizes. Surprisingly, double-knockout mice are viable, with subtle alterations in cranial bone morphology that are reminiscent of mutation in another Wnt/β-catenin antagonist,axin2 . Our data show thatnkd function in the mouse is dispensable for embryonic development.