Newslet14.pdf

Newsletter
Deutschen Gesellschaft für Neurogenetik
8th Workshop Neurogenetics in
Germany, 7th Annual Meeting of
Kunst et al. have mapped a gene locus in a sclerosis (ALS) that greatly delays disease The 7th annual meeting of the society of only disease gene identified in autosomal found that disease onset is dependent on While disease develops at about 100 days retardation“, „ion channel diseases“, greatly delayed (143 days to >2 years) in diseases“, „paraplegias“, „muscular dystrophies“ and „embryonic stem cells C57Bl6/129Sv. Performing linkage analyses in neurological diseases“. Details and in a large pedigree originating from the magdeburg.de/fme/institute/ihg/tagung.
murine chromosome 13. Since the interval motor neuron) and several copies of Naip (neuronal apoptosis inhibitory protein) the Mapping of modifier gene in mouse
model of ALS. In monogenic disorders
Kunst, CB, Messer L, Gordon J, Haines J, Patterson D: can result in highly variable phenotypes. Genetic mapping of a mouse modifier gene that can prevent ALS onset. Genomics 70: 181-189 (2000). Growing number of inducible
transgenic mouse models. Although the
every carrier of a mutation) and variable models for human diseases is continuously growing, inducible models overexpressing a specific transgene are rather rare. The neuropathy. They also used the tetracycline when it is duplicated and therefore present started. It might therefore also be useful patient. In their mice, Perea and colleagues to estimate the efficiency of therapeutic were able to generate an inducible model Turning off PMP22 transgene expression by administration of tetracycline resulted in the correction of demyelination that started repeatedly, the phenotype developed again in the mice clearly indicating that pmp22 therapeutic interventions downregulating dystrophin in mdx mice (Ahmad et al. the long road to develop and identify drugs Ahmad A, Brinson M, Hodges BL, Chamberlain JS, and Amalfitano A (2000) Mdx mice inducibly expressing dystrophin provide insights into the potential of gene therapy for Duchenne muscular dystrophy. Hum Mol Gossen M and Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline- expressed dystrophin is localized at the responsive promoters. Proc Natl Acad Sci USA Perea J, Robertson A, Tolmachova T, Muddle J, King of expression is far more effective when RHM, Ponsford S, Thomas PK, and Huxley C (2001) Induced myelination and demyelination in a (expression at later stages did not lead conditional mouse model of Charcot-Marie-Tooth disease type 1A. Hum Mol Genet 10: 1007-1018 Yamamoto A, Lucas JJ, and Hen R (2000) Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease. Cell 101: 57-66 HIF regulation of mutant VHL product
might also be beneficial in DMD patients is preserved in type 2C
(pheochromocytoma only) von
Hippel-Lindau disease. Von Hippel-
existing vectors occurs over time. Perea Lindau (VHL) disease is a rare hereditary spinal, and medullary hemangioblastomas, S80G). Two of the mutations studied were distinguished clinically. Type 1 denotes groups found that the type C mutations are still capable of downregulating HIF1 to fibronectin binding. Their findings suggest angioblastomas and renal cell carcinomas but not of pheochromocytomas. It appears occur in the presence of both renal cell result in both defective HIF1 regulation and gene. Its product (pVHL) associates with Hoffman MA, Ohh M, Yang H, Klco JM, Ivan M, Kaelin WG (2001) von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF. Hum Mol Genet 10: 1019-1027 towards proteasomal degradation) of subunit HIFα in the presence of Clifford SC, Cockman ME, Smallwood AC, Mole DR, Woodward ER, Maxwell PH, Ratcliffe PJ, Maher ER (2001) Contrasting effects on HIF-1α regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau factor), PDF B (platelet-derived growth factor B chain), and TGFα Genotype-phenotype correlations in
tuberous sclerosis. Tuberous sclerosis is
high levels of HIF1 and its target genes. epileptic seizures, and mental retardation. Two gene loci have been identified, i.e. interacting with fibronectin, and a role TSC1 on chromosome 9q34, and TSC2 on heterozygosity (LOH) analyses suggest that both TSC1 and TSC2 can function as tumor encoded by TSC1 is referred to as hamartin and that encoded by TSC2 as tuberin. In a patients with mutations at TSC1 and TSC2, at TSC1 and in 158 at TSC2. Although TSC1 patients had fewer seizures and than patients with mutations at TSC2. common than in TSC2 patients. Given hamartomas and angiolipomas in TSC1, common in TSC1 than in TSC2. Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy Y-S, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ (2001) Mutational analysis in a cohort of 224 tuberous sclerosis pateints indicates increased seerity of TSC2, compared with TSC1, Disease in multiple organs. Am J Hum Genet 68: 64-80 (2001)

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