Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2

Shu Zhang, Tolga Çagatay, Manami Amanai, Mei Zhang, Janine Kline, Diego H. Castrillon, Raheela Ashfaq, Orhan K. Öz, Keith A. Wharton

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4454-4464
Number of pages11
JournalMolecular and Cellular Biology
Volume27
Issue number12
DOIs
StatePublished - Jun 2007

Fingerprint

Catenins
Wnt Signaling Pathway
Mutation
Embryonic Development
Wnt Proteins
Litter Size
Neomycin
Drosophila melanogaster
Knockout Mice
Diptera
Exons
Fruit
Carrier Proteins
Proteins
Homeostasis
Alleles
Bone and Bones
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2. / Zhang, Shu; Çagatay, Tolga; Amanai, Manami; Zhang, Mei; Kline, Janine; Castrillon, Diego H.; Ashfaq, Raheela; Öz, Orhan K.; Wharton, Keith A.

In: Molecular and Cellular Biology, Vol. 27, No. 12, 06.2007, p. 4454-4464.

Research output: Contribution to journalArticle

Zhang, S, Çagatay, T, Amanai, M, Zhang, M, Kline, J, Castrillon, DH, Ashfaq, R, Öz, OK & Wharton, KA 2007, 'Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2', Molecular and Cellular Biology, vol. 27, no. 12, pp. 4454-4464. https://doi.org/10.1128/MCB.00133-07
Zhang, Shu ; Çagatay, Tolga ; Amanai, Manami ; Zhang, Mei ; Kline, Janine ; Castrillon, Diego H. ; Ashfaq, Raheela ; Öz, Orhan K. ; Wharton, Keith A. / Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 12. pp. 4454-4464.
@article{1bdcc47ea7d043aebcce099243bb9042,
title = "Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2",
abstract = "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.",
author = "Shu Zhang and Tolga {\cC}agatay and Manami Amanai and Mei Zhang and Janine Kline and Castrillon, {Diego H.} and Raheela Ashfaq and {\"O}z, {Orhan K.} and Wharton, {Keith A.}",
year = "2007",
month = "6",
doi = "10.1128/MCB.00133-07",
language = "English (US)",
volume = "27",
pages = "4454--4464",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "12",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=34250209861&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250209861&partnerID=8YFLogxK

U2 - 10.1128/MCB.00133-07

DO - 10.1128/MCB.00133-07

M3 - Article

VL - 27

SP - 4454

EP - 4464

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 12

ER -