27 research outputs found
Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth
Ciliary neurotrophic factor (CNTF) supports motor neuron survival in vitro and in mouse models of motor neuron degeneration and was considered a candidate for the muscle-derived neurotrophic activity that regulates motor neuron survival during development. However, CNTF expression is very low in the embryo, and CNTF gene mutations in mice or human do not result in notable abnormalities of the developing nervous system. We have generated and directly compared mice containing null mutations in the genes encoding CNTF or its receptor (CNTFRα). Unlike mice lacking CNTF, mice lacking CNTFRα die perinatally and display severe motor neuron deficits. Thus, CNTFRα is critical for the developing nervous system, most likely by serving as a receptor for a second, developmentally important, CNTF-like ligand
Sex dependent transmission of Beckwith-Wiedemann syndrome associated with a reciprocal translocation t(9;11)(p11.2;p15.5).
Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4
Nerve growth factor and other neurotrophins signal to neurons through the Trk family of receptor tyrosine kinases. TrkB is relatively promiscuous in vitro, acting as a receptor for brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT4) and, to a lesser extent, NT3. Mice lacking TrkB show a more severe phenotype than mice lacking BDNF, suggesting that TrkB may act as a receptor for additional ligands in vivo. To explore this possibility, we generated mice lacking NT4 or BDNF as well as mice lacking both neurotrophins. Unlike mice lacking other Trks or neurotrophins. NT4-deficient mice are long-lived and show no obvious neurological defects. Analysis of mutant phenotypes revealed distinct neuronal populations with different neurotrophin requirements. Thus vestibular and trigeminal sensory neurons require BDNF but not NT4, whereas nodose-petrosal sensory neurons require both BDNF and NT4. Motor neurons, whose numbers are drastically reduced in mice lacking TrkB, are not affected even in mice lacking both BDNF and NT4. These results suggest that another ligand, perhaps NT3, does indeed act on TrkB in vivo
The murine leukemia inhibition factor gene (Lif) is located on proximal Chromosome 11, not Chromosome 13
Parental allele specific methylation of the human insulin-like growth factor II gene and Beckwith-Wiedemann syndrome.
Molecular Modeling and Conformational Analysis of MuSK Protein
Part 8: First Workshop on Algorithms for Data and Text Mining in Bioinformatics (WADTMB 2012)International audienceMuscle-specific kinase is a crucial receptor tyrosine kinase required for the development and function of neuromuscular junction. Although many protein domains have already been modeled with crystallographic techniques in various organisms, a single model for the whole human structure is not yet available. A model of the entire protein was constructed by using two parallel Homology Modeling approaches, one unsupervised and one driven by the user. In addition, by applying Molecular Dynamics simulations the present study provides further insights on the structure, and the intermolecular interactions of the protein were examined. The expected semi rigid globular form of the protein was confirmed and in addition a hydrophobic core and a hydrogen bond network that enhances the stability of the molecule were observed. Furthermore, these calculations identified an intriguing rotation of Ig domains and this finding sets the base for additional hypothesis and further investigation