Homozygosity for the<i>Min</i>allele of<i>Apc</i>results in disruption of mouse development prior to gastrulation

Moser, Amy R.; Shoemaker, Alexander R.; Connelly, Camille S.; Clipson, Linda; Gould, Karen A.; Luongo, Cindy; Dove, William F.; Siggers, Pamela; Gardner, Richard L.

doi:10.1002/aja.1002030405

Cited by 145 publications

(88 citation statements)

References 28 publications

(35 reference statements)

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“…It produces a stable truncated protein of 850 amino acids that lacks all ␤-catenin binding and other regulatory motifs (Su et al, 1992), leading to complete inability to bind and downregulate ␤-catenin, thus producing constitutively active ␤-catenin signaling. Complete loss of function of the Apc gene in Apc Min/Min embryos results in block of development at the 5.5-6.5 dpc stage and mutant embryos fail to form a pro-amniotic cavity or a primitive streak (Moser et al, 1995). This suggests that the patterning of the earliest phases of PD axis formation may also be susceptible to elevated ␤-catenin activity.…”

Section: Introductionmentioning

confidence: 92%

Disruption of early proximodistal patterning and AVE formation inApcmutants

Chazaud

Rossant

2006

Development

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In the postimplantation mouse embryo, axial patterning begins with the restriction of expression of a set of genes to the distal visceral endoderm (DVE). This proximodistal (PD) axis is subsequently transformed into an anteroposterior axis as the VE migrates anteriorly to form the anterior visceral endoderm (AVE). Both Nodal and Wnt signaling pathways are involved in these events. We show here that loss of function in the adenomatous polyposis coli gene (Apc) leads to constitutive ␤-catenin activity that induces a proximalization of the epiblast with the activation of a subset of posterior mesendodermal genes, and loss of ability to induce the DVE. The loss of some DVE genes such as Hex and goosecoid is rescued in chimeras where only the epiblast was wild type; however, these DVE markers were no longer restricted distally but covered the entire epiblast. Thus, the Apc gene is needed in both embryonic and extra-embryonic lineages for normal PD patterning around implantation, suggesting that early restricted activation of the Wnt pathway may be important for initiating axial asymmetries. In addition, we found that nuclear ␤-catenin and other molecular markers are asymmetrically expressed by 4.5 days.

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Section: Introductionmentioning

confidence: 92%

Disruption of early proximodistal patterning and AVE formation inApcmutants

Chazaud

Rossant

2006

Development

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“…Furthermore, Apc +/Min mice have a low penetrance of extracolonic-manifestations such as mammary tumors, desmoids or cysts (Moser et al, 1993, Smits et al, 1998, Halberg et al, 2000. Homozygosity for this mutation leads to embryonic lethality at very early stages of gestation (6.5 dpc) (Moser et al, 1995). Accordingly, a similar mouse model, Apc ∆716 , carrying a targeted truncated mutation at codon 716 is also characterized by multiple intestinal tumors and no extra-intestinal manifestations (Oshima et al, 1995).…”

Section: Apc Dosage Effects In Tumorigenesismentioning

confidence: 99%

APC dosage effects in tumorigenesis and stem cell differentiation

Gaspar¹,

Fodde²

2004

Int. J. Dev. Biol.

111

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“…Die by 4 Weeks of Age-Because global inactivation of either the ␤-catenin gene (14,15) or Apc (16,17) results in early embryonic death, we crossed mice containing conditionally inactivatable alleles of ␤-catenin (␤-catenin-flox) (18) or Apc (Apc-flox) (19) to mice expressing cre under the control of the osteocalcin (OC) promoter (20) to disrupt these genes in osteoblasts. Previous analysis of the OC-cre strain via crossing it to strains carrying cre reporter transgenes indicated that expression of cre recombinase was specific to cells of the osteoblast lineage with no detectable expression or function in other cell lineages (20).…”

Section: Mice With Osteoblast-specific Deletions Of ␤-Catenin or Apcmentioning

confidence: 99%

Essential Role of β-Catenin in Postnatal Bone Acquisition

Holmen

Zylstra

Mukherjee

et al. 2005

Journal of Biological Chemistry

553

508

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Mutations in the Wnt co-receptor LRP5 alter bone mass in humans, but the mechanisms responsible for Wnts actions in bone are unclear. To investigate the role of the classical Wnt signaling pathway in osteogenesis, we generated mice lacking the ␤-catenin or adenomatous polyposis coli (Apc) genes in osteoblasts. Loss of ␤-catenin produced severe osteopenia with striking increases in osteoclasts, whereas constitutive activation of ␤-catenin in the conditional Apc mutants resulted in dramatically increased bone deposition and a disappearance of osteoclasts. In vitro, osteoblasts lacking the ␤-catenin gene exhibited impaired maturation and mineralization with elevated expression of the osteoclast differentiation factor, receptor activated by nuclear factor-B ligand (RANKL), and diminished expression of the RANKL decoy receptor, osteoprotegerin. By contrast, Apc-deficient osteoblasts matured normally but demonstrated decreased expression of RANKL and increased osteoprotegerin. These findings suggest that Wnt/␤-catenin signaling in osteoblasts coordinates postnatal bone acquisition by controlling the differentiation and activity of both osteoblasts and osteoclasts.

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Homozygosity for theMinallele ofApcresults in disruption of mouse development prior to gastrulation

Abstract: ABSTRACT

Cited by 145 publications

References 28 publications

Disruption of early proximodistal patterning and AVE formation inApcmutants

Disruption of early proximodistal patterning and AVE formation inApcmutants

APC dosage effects in tumorigenesis and stem cell differentiation

Essential Role of β-Catenin in Postnatal Bone Acquisition

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