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Insertional Mutation (insertional + mutation)
Selected AbstractsCalcium/calmodulin-dependent serine protein kinase and mental retardation,ANNALS OF NEUROLOGY, Issue 4 2009Yi-Ping Hsueh PhD Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase protein family. The members of this protein family function as multiple domain adaptor proteins originally identified at cell junctions and synapses. Insertional mutations or targeted disruption of the CASK gene in mice results in neonatal lethality, indicating an important role for CASK in development. Recently, several reports have also indicated that mutations in the human CASK gene result in X-linked malformations of the brain and mental retardation. At the molecular level, many studies indicate that CASK is critical for synapse formation at both presynaptic and postsynaptic junctions, and in the regulation of gene expression. The known molecular functions of CASK explain, at least partially, mental retardation and brain developmental defects in patients. In this review, recent findings about CASK are summarized and discussed. Ann Neurol 2009;66:438,443 [source] Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin,HUMAN MUTATION, Issue 6 2008Shweta Singh Abstract Lafora disease (LD) is a fatal form of teenage-onset autosomal recessive progressive myoclonus epilepsy. LD is more common among geographic isolates and in populations with a higher rate of consanguinity. Mutations in two genes, EPM2A encoding laforin phosphatase, and NHLRC1 encoding malin ubiquitin ligase, have been shown to cause the LD. We describe here a systematic analysis of the EPM2A and the NHLRC1 gene sequences in 20,LD families from the Indian population. We identified 12 distinct mutations in 15,LD families. The identified novel mutations include 4 missense mutations (K140N, L310W, N148Y, and E210,K) and a deletion of exon 3 for EPM2A, and 4 missense mutations (S22R, L279P, L279P, and L126P) and a single base-pair insertional mutation (612insT) for NHLRC1. The EPM2A gene is known to encode two laforin isoforms having distinct carboxyl termini; a major isoform localized in the cytoplasm, and a minor isoform that targeted the nucleus. We show here that the effect of the EPM2A gene mutation L310W was limited to the cytoplasmic isoform of laforin, and altered its subcellular localization. We have also analyzed the impact of NHLRC1 mutations on the subcellular localization of malin. Of the 6 distinct mutants tested, three targeted the nucleus, one formed perinuclear aggregates, and two did not show any significant difference in the subcellular localization as compared to the wild-type malin. Our results suggest that the altered subcellular localization of mutant proteins of the EPM2A and NHLRC1 genes could be one of the molecular bases of the LD phenotype. © 2008 Wiley-Liss, Inc. [source] A novel insertional mutation in Connexin 32 gene causes demyelinating polyneuropathy with predominantly motor axonal lossJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2004Lan Zhou [source] piggyBac transformation of the New World screwworm, Cochliomyia hominivorax, produces multiple distinct mutant strainsMEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2004M. L. Allen Abstract., Sterile insect technique (SIT) programs are designed to eradicate pest species by releasing mass-reared, sterile insects into an infested area. The first major implementation of SIT was the New World Screwworm Eradication Program, which successfully eliminated the New World screwworm (NWS), Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae), from the Continental US, Mexico and much of Central America. Ionizing radiation is currently used for sterilization, but transgenic insect techniques could replace this method, providing a safer, more cost-effective alternative. Genetic transformation methods have been demonstrated in NWS, and verified by Southern blot hybridization, PCR and sequencing of element insertion junctions. A lethal insertional mutation and enhancer detection-like phenotypic expression variations are presented and discussed. In addition to supporting the eradication efforts, transformation methods offer potential means to identify genes and examine gene function in NWS. [source] Expression of the Pho regulon negatively regulates biofilm formation by Pseudomonas aureofaciens PA147-2MOLECULAR MICROBIOLOGY, Issue 2 2001Russell D. Monds We report the isolation of insertional mutations to the pstC and pstA genes of the phosphate-specific transport (pst) operon that results in loss of biofilm formation by Pseudomonas aureofaciens PA147-2. Consistent with the known roles of the Pst system in Escherichia coli and Pseudomonas aeruginosa, both P. aureofaciens pst mutants were demonstrated to have defects in inorganic phosphate (Pi) transport and repression of Pho regulon expression. Subsequently, biofilm formation by the wild type was shown to require a threshold concentration of extracellular Pi. The two-component regulatory pair PhoR/PhoB is responsible for upregulation of Pho regulon expression in response to Pi -limiting environments. By generating phoR mutants that were unable to express the Pho regulon, we were able to restore biofilm formation by P. aureofaciens in Pi -limiting conditions. This result suggests that gene(s) within the Pho regulon act to regulate biofilm formation negatively in low-Pi environments, and that phoR mutations uncouple PA147-2 from such regulatory constraints. Furthermore, the inability of pst mutants to repress Pho regulon expression accounts for their inability to form biofilms in non-limiting Pi environments. Preliminary evidence suggests that the Pst system is also required for antifungal activity by PA147-2. During phenotypic analysis of pst mutants, we also uncovered novelties in relation to Pi assimilation and Pho regulon control in P. aureofaciens. [source] | |||||||||||||