Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2.
Gradients of Wnt/beta-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/beta-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 nkd(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/beta-catenin antagonist, axin2. Our data show that nkd function in the mouse is dispensable for embryonic development.
Zhang
Shu
S
Laboratory of Molecular Pathology, Department of Pathology, Dallas, TX 75390-9072, USA.
Cagatay
Tolga
T
Amanai
Manami
M
Zhang
Mei
M
Kline
Janine
J
Castrillon
Diego H
DH
Ashfaq
Raheela
R
Oz
Orhan K
OK
Wharton
Keith A
KA
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors*; D000483:Alleles; D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics*; D003433:Crosses, Genetic; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D047108:Embryonic Development; D005091:Exons; D005328:Fetal Viability / Q000235:genetics*; D006720:Homozygote; D007763:Lac Operon / Q000235:genetics; D008098:Litter Size / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010750:Phosphoproteins / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; C424446:Nkd1 protein, mouse; D010750:Phosphoproteins; D051153:Wnt Proteins; C000606588:dsh protein, Drosophila