Targeted disruption of the intracellular domain of receptor FgfrL1 in mice.


Autoria(s): Bluteau, Gilles; Zhuang, Lei; Amann, Ruth; Trueb, Beat
Data(s)

2014

Resumo

FgfrL1 is the fifth member of the fibroblast growth factor receptor (Fgfr) family. Studies with FgfrL1 deficient mice have demonstrated that the gene plays an important role during embryonic development. FgfrL1 knock-out mice die at birth as they have a malformed diaphragm and lack metanephric kidneys. Similar to the classical Fgfrs, the FgfrL1 protein contains an extracellular part composed of three Ig-like domains that interact with Fgf ligands and heparin. However, the intracellular part of FgfrL1 is not related to the classical receptors and does not possess any tyrosine kinase activity. Curiously enough, the amino acid sequence of this domain is barely conserved among different species, with the exception of three motifs, namely a dileucine peptide, a tandem tyrosine-based motif YXXΦ and a histidine-rich sequence. To investigate the function of the intracellular domain of FgfrL1, we have prepared genetically modified mice that lack the three conserved sequence motifs, but instead contain a GFP cassette (FgfrL1ΔC-GFP). To our surprise, homozygous FgfrL1ΔC-GFP knock-in mice are viable, fertile and phenotypically normal. They do not exhibit any alterations in the diaphragm or the kidney, except for a slight reduction in the number of glomeruli that does not appear to affect life expectancy. In addition, the pancreas of both FgfrL1ΔC-GFP knock-in and FgfrL1 knock-out mice do not show any disturbances in the production of insulin, in contrast to what has been suggested by recent studies. Thus, the conserved motifs of the intracellular FgfrL1 domain are dispensable for organogenesis and normal life. We conclude that the extracellular domain of the protein must conduct the vital functions of FgfrL1.

Formato

application/pdf

Identificador

http://boris.unibe.ch/64174/2/http___www.plosone.org_article_fetchObject.action_uri%3Dinfo_doi_10.1371_journal.pone.0105210%26representation%3DPDF.pdf

Bluteau, Gilles; Zhuang, Lei; Amann, Ruth; Trueb, Beat (2014). Targeted disruption of the intracellular domain of receptor FgfrL1 in mice. PLoS ONE, 9(8), e105210. Public Library of Science 10.1371/journal.pone.0105210 <http://dx.doi.org/10.1371/journal.pone.0105210>

doi:10.7892/boris.64174

info:doi:10.1371/journal.pone.0105210

info:pmid:25126760

urn:issn:1932-6203

Idioma(s)

eng

Publicador

Public Library of Science

Relação

http://boris.unibe.ch/64174/

Direitos

info:eu-repo/semantics/openAccess

Fonte

Bluteau, Gilles; Zhuang, Lei; Amann, Ruth; Trueb, Beat (2014). Targeted disruption of the intracellular domain of receptor FgfrL1 in mice. PLoS ONE, 9(8), e105210. Public Library of Science 10.1371/journal.pone.0105210 <http://dx.doi.org/10.1371/journal.pone.0105210>

Palavras-Chave #610 Medicine & health
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/publishedVersion

PeerReviewed