Inducing mutations in the mouse genome with the chemical mutagen ethylnitrosourea

When compared to other model organisms whose genome is sequenced, the number of mutations identified in the mouse appears extremely reduced and this situation seriously hampers our understanding of mammalian gene function(s). Another important consequence of this shortage is that a majority of human genetic diseases still await an animal model. To improve the situation, two strategies are currently used: the first makes use of embryonic stem cells, in which one can induce knockout mutations almost at will; the second consists of a genome-wide random chemical mutagenesis, followed by screening for mutant phenotypes and subsequent identification of the genetic alteration(s). Several projects are now in progress making use of one or the other of these strategies. Here, we report an original effort where we mutagenized BALB/c males, with the mutagen ethylnitrosourea. Offspring of these males were screened for dominant mutations and a three-generation breeding protocol was set to recover recessive mutations. Eleven mutations were identified (one dominant and ten recessives). Three of these mutations are new alleles (Otop1mlh, Foxn1sepe and probably rodador) at loci where mutations have already been reported, while 4 are new and original alleles (carc, eqlb, frqz, and Sacc). This result indicates that the mouse genome, as expected, is far from being saturated with mutations. More mutations would certainly be discovered using more sophisticated phenotyping protocols. Seven of the 11 new mutant alleles induced in our experiment have been localized on the genetic map as a first step towards positional cloning

Transcriptome of the wistar audiogenic rat (WAR) strain following audiogenic seizures

FAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe Wistar Audiogenic Rat (WAR) is a model whose rats are predisposed to develop seizures following acoustic stimulation. We aimed to establish the transcriptional profile of the WAR model, searching for genes that help in understanding the molecular mech1472231FAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOEDT -193/092009/53444-

Gene Expression Profiling In Genetic Animal Models Of Provide Elements To Unveil The Molecular Mechanisms Underlying Epileptogenesis In Rodents [a Caracterização Do Perfil De Expressão Gênica Em Larga Escala Em Modelos Genéticos De Epilepsia Fornece Elementos Para Entender Os Mecanismos Envolvidos Na Epileptogênese Em Roedores]

Objective: The objective of this study was to characterize and compare the genetic profile of two rodent models of epilepsy (Wistar Audiogenic Rat - WAR and rats with generalized epilepsy with absence seizures-GEAS) using gene expression analysis Methods: We used microarray technology for gene expression analysis. Results: The analysis of gene expression profiles in WAR showed among genes up-regulated Neurod1, involved in the development of the cochlear duct. In addition, we found significant differences in gene expression of Apbb1, Foxg1 and Scn1A. GEAS rats had differentially expressed genes related to the development of central nervous system, as well as genes involved in the MAPK pathway, transcription factors, neuronal migration and apoptosis. Conclusion: This study may help to clarify the underlying molecular mechanism that leads to the predisposition to seizures in these animals. Our results indicate the activation of distinct molecular pathways in both models.1825052Aicard, J., Course and prognosis of certain chidhood epilepsies with predominantly myoclonic seizures (1980) Advances in Epileptology. The Xth Epilepsy International Symposim, pp. 159-163. , Wada JA, Penry JK e cols. New York: RavemAndré, E.S., Electrophysiological characterization of a new form of spontaneous epilepsy in Wistar rats (1999) Epilepsia, 40 (SUPPL. 2)Bruno-Neto, R., Caracterização de uma nova forma de epilepsia espontânea em ratos Wistar (1999) XIV FESBE, AnaisBruno-Neto, R., André, E.S., Pellarin, L., Hilário, F.K., Valle, A.C., Timo-Iaria, C., Electrophysiological characterization of a new form of spontaneous epilepsy in Wistar rats (1999) 23rd International Epilepsy Congress, Prague, Czech RepublicDoretto, M.C., Fonseca, C.G., Lobo, R.B., Terra, V.C., Oliveira, J.A., Garcia-Cairasco, N., Quantitative study of the response to genetic selection of the WistarAudiogenic Rat strain (WAR) (2003) Behav Genet, 33 (1), pp. 33-42Garcia-Cairasco, N., Sabbatini, R., Role of the substantianigra in audiogenic seizures: A neuroethological analysis in the rat (1983) Braz J Med Biol Res, 16 (2), pp. 171-183Gitaí, D.L., Martinelli, H.N., Valente, V., Pereira, M.G., Oliveira, J.A., Elias, C.F., Bittencourt, J.C., Paçó-Larson, M.L., Increased expression of GluR2-flip in the hippocampus of the Wistaraudiogenic rat strain after acute and kindled seizures (2010) Hippocampus, 20, pp. 125-133Jobe, P.C., Brown, R.D., Dailey, J.W., Effect of Ro 4-1284 on audiogenic seizure susceptibility and intensity in epilepsy-prone rats (1981) Life Sci, 28 (18), pp. 2031-2038Kovács, Z., Suppression of spike-wave discharge activity and c-fos expression by2-methyl-4-oxo-3H-quinazoline-3-acetyl piperidine (Q5) in vivo (2007) Neuroscience Letters, 423, pp. 73-77Mesquita, F., Aguiar, J.F., Oliveira, J.A., Garcia-Cairasco, N., Varanda, W.A., Electrophysiological properties of cultured hippocampal neurons from WistarAudiogenic rats (2005) Brain Res Bul, 65, pp. 177-183Moraes, M.F., Galvis-Alonso, O.Y., Garcia-Cairasco, N., Audiogenic kindling in the Wistar rat: A potential model for recruitment of limbic structures (2000) Epilepsy Research, 39, pp. 251-259Nunes, P.V., Valle, A.C., Timo-Iaria, C., Epileptogenic potentials recorded from the cerebellar cortex in rats (1999) Epilepsia, 40, p. 132. , 23th International Epilepsy Congress, Prague, Czech Republi