2024-03-28T21:07:11Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/594452021-05-24T12:31:21Zcom_10261_133com_10261_1col_10261_386
DIGITAL.CSIC
author
Viosca, José
author
Schuhmacher, Alberto J.
author
Guerra, Carmen
author
Barco, Ángel
2012-11-05T10:47:10Z
2012-11-05T10:47:10Z
2009
Genes, Brain and Behavior 8(1): 60- 71 (2009)
http://hdl.handle.net/10261/59445
10.1111/j.1601-183X.2008.00443.x
18823404
Costello syndrome (CS) is a rare congenital disorder caused by germline activation of H-Ras oncogenes. A mouse model of CS generated by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in embryonic stem (ES) cells has been recently described. These mice phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. We investigated here their neurological and behavioral phenotype. The analysis of H-RasG12V mice revealed phenotypes that resembled the hyperemotivity, hypersensibility and cognitive impairments observed in children with CS. Stronger neurological deficits were found in the analysis of mice homozygous for this mutation than in the analysis of heterozygous mice, suggesting the existence of a gene dose effect. These mice represent the first mouse model for CS, offering an experimental tool to study the molecular and physiological alterations underlying the neurological manifestations of CS and to test new therapies aimed at preventing or ameliorating the cognitive and emotional impairments associated to this condition.
eng
openAccess
Germline expression of H-RasG12V causes neurological deficits associated to Costello syndrome
artículo
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URL
https://digital.csic.es/bitstream/10261/59445/3/Germ%20line.pdf
File
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Germ line.pdf
URL
https://digital.csic.es/bitstream/10261/59445/5/Germ%20line.pdf.txt
File
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Germ line.pdf.txt