TY - JOUR
T1 - Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2
AU - Zhang, Shu
AU - Çagatay, Tolga
AU - Amanai, Manami
AU - Zhang, Mei
AU - Kline, Janine
AU - Castrillon, Diego H.
AU - Ashfaq, Raheela
AU - Öz, Orhan K.
AU - Wharton, Keith A.
PY - 2007/6
Y1 - 2007/6
N2 - Gradients of Wnt/β-catenin signaling coordinate development and physiological homeostasis in metazoan animals. Proper embryonic development of the fruit fly Drosophila 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 two nkd homologs, nkd1 and nkd2, whose encoded proteins can bind Dsh homologs (the Dvl proteins) and inhibit Wnt signaling. To determine whether nkd genes are necessary for murine development, we replaced nkd exons that encode Dvl-binding sequences with IRES-lacZ/neomycin cassettes. Mutants homozygous for each nkdlacZ 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 that nkd function in the mouse is dispensable for embryonic development.
AB - Gradients of Wnt/β-catenin signaling coordinate development and physiological homeostasis in metazoan animals. Proper embryonic development of the fruit fly Drosophila 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 two nkd homologs, nkd1 and nkd2, whose encoded proteins can bind Dsh homologs (the Dvl proteins) and inhibit Wnt signaling. To determine whether nkd genes are necessary for murine development, we replaced nkd exons that encode Dvl-binding sequences with IRES-lacZ/neomycin cassettes. Mutants homozygous for each nkdlacZ 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 that nkd function in the mouse is dispensable for embryonic development.
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U2 - 10.1128/MCB.00133-07
DO - 10.1128/MCB.00133-07
M3 - Article
C2 - 17438140
AN - SCOPUS:34250209861
SN - 0270-7306
VL - 27
SP - 4454
EP - 4464
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 12
ER -