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Lallemand, Yvan; Luria, Victor; Haffner-Krausz, Rebecca; Lonai, Peter

doi:10.1023/a:1008868325009

Cited by 362 publications

(160 citation statements)

References 17 publications

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“…4. Germ line-transmitting chimeras of two independent clones were obtained, and the floxed neo cassette was removed in vivo by mating to the PGK-Cre m deleter strain (15).…”

Section: Methodsmentioning

confidence: 99%

A gain-of-function mutation of Fgfr2c demonstrates the roles of this receptor variant in osteogenesis

Eswarakumar

Horowitz²,

Locklin³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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200

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The b and c variants of fibroblast growth factor receptor 2 (FGFR2) differ in sequence, binding specificity, and localization. Fgfr2b, expressed in epithelia, is required for limb outgrowth and branching morphogenesis, whereas the mesenchymal Fgfr2c variant is required by the osteocyte lineage for normal skeletogenesis. Gain-of-function mutations in human FGFR2c are associated with craniosynostosis syndromes. To confirm and extend this evidence, we introduced a Cys342Tyr replacement into Fgfr2c to create a gain-of-function mutation equivalent to a mutation in human Crouzon and Pfeiffer syndromes.

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“…4. Germ line-transmitting chimeras of two independent clones were obtained, and the floxed neo cassette was removed in vivo by mating to the PGK-Cre m deleter strain (15).…”

Section: Methodsmentioning

confidence: 99%

A gain-of-function mutation of Fgfr2c demonstrates the roles of this receptor variant in osteogenesis

Eswarakumar

Horowitz²,

Locklin³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

200

219

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“…The shRNA transcription is driven in mice by the transgene rtTA3 in the presence of dox, of which spatial expression is restricted courtesy of a loxP-stop-loxP (LSL) cassette (this model is termed LSL-ATG5i mice). To generate a second version of the mouse model, wherein Atg5 can be ubiquitously knocked down, we crossed the LSL-ATG5i mouse to a Pgk1-Cre -expressing strain [15]. This resulted in germ-line excision of the LSL ‘STOP cassette’, which was passed on to subsequent generations, while the Pgk1-Cre was rapidly bred out (ATG5i mice).…”

Section: Resultsmentioning

confidence: 99%

A novel Atg5-shRNA mouse model enables temporal control of Autophagy in vivo

et al. 2018

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Macroautophagy/autophagy is an evolutionarily conserved catabolic pathway whose modulation has been linked to diverse disease states, including age-associated disorders. Conventional and conditional whole-body knockout mouse models of key autophagy genes display perinatal death and lethal neurotoxicity, respectively, limiting their applications for in vivo studies. Here, we have developed an inducible shRNA mouse model targeting Atg5, allowing us to dynamically inhibit autophagy in vivo, termed ATG5i mice. The lack of brain-associated shRNA expression in this model circumvents the lethal phenotypes associated with complete autophagy knockouts. We show that ATG5i mice recapitulate many of the previously described phenotypes of tissue-specific knockouts. While restoration of autophagy in the liver rescues hepatomegaly and other pathologies associated with autophagy deficiency, this coincides with the development of hepatic fibrosis. These results highlight the need to consider the potential side effects of systemic anti-autophagy therapies.

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“…Two of eight correctly recombined ES clones were used to make chimeras. The floxed neocassette was removed in vivo from the germ-line transmitting chimeras by mating to the PGK-Cre m transgenic deleter strain (29).…”

Section: Methodsmentioning

confidence: 99%

Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis

Eswarakumar¹,

Özcan²,

Lew³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Craniosynostosis, the fusion of one or more of the sutures of the skull vault before the brain completes its growth, is a common (1 in 2,500 births) craniofacial abnormality, Ϸ20% of which occurrences are caused by gain-of-function mutations in FGF receptors (FGFRs). We describe a genetic and pharmacological approach for the treatment of a murine model system of Crouzon-like craniosynostosis induced by a dominant mutation in Fgfr2c. Using genetically modified mice, we demonstrate that premature fusion of sutures mediated by Crouzon-like activated Fgfr2c mutant is prevented by attenuation of signaling pathways by selective uncoupling between the docking protein Frs2␣ and activated Fgfr2c, resulting in normal skull development. We also demonstrate that attenuation of Fgfr signaling in a calvaria organ culture with an Fgfr inhibitor prevents premature fusion of sutures without adversely affecting calvaria development. These experiments show that attenuation of FGFR signaling by pharmacological intervention could be applied for the treatment of craniosynostosis or other severe bone disorders caused by mutations in FGFRs that currently have no treatment.bone disorders ͉ cell signaling ͉ cell surface receptors ͉ protein kinases ͉ skull development

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Untitled

Cited by 362 publications

References 17 publications

A gain-of-function mutation of Fgfr2c demonstrates the roles of this receptor variant in osteogenesis

A gain-of-function mutation of Fgfr2c demonstrates the roles of this receptor variant in osteogenesis

A novel Atg5-shRNA mouse model enables temporal control of Autophagy in vivo

Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis

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