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El receptor del factor de crecimiento tipo 2 similar a la insulina del ratón está impreso y estrechamente vinculado
D P Barlow1, R Stöger, B G Herrmann
1Research Institute for Molecular Pathology, Vienna, Austria.
Nature
|January 3, 1991
Resumen
La mutación de efecto materno Tme causa la muerte embrionaria en ratones. Los investigadores identificaron el gen del receptor del factor de crecimiento similar a la insulina tipo 2 (Igf2r) como impreso y vinculado a Tme, ofreciendo información sobre el imprinting genómico.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Genética La genética.
- La genómica es la genómica.
Sus antecedentes:
- El efecto materno asociado a T (Tme) es la única mutación de efecto materno identificada en ratones, que conduce a la letalidad embrionaria.
- La impresión genómica, donde la expresión génica depende del origen parental, se conoce en ratones, pero los genes impresos permanecen en gran medida sin caracterizar.
- Se desconoce la ubicación precisa del locus Tme, aunque está localizado en una región de 1-cM en el cromosoma 17 utilizando mutantes de deleción.
Objetivo del estudio:
- Para clonar genes impresos en el locus Tme.
- Para investigar la base genética de la letalidad embrionaria mediada por Tme.
Principales métodos:
- Se utilizaron mutantes de deleción del cromosoma 17 (Thp y tLub2) para reducir el locus Tme.
- Empleado electroforesis en gel de campo pulsado con sondas para Igf2r, Sod-2, Plg y Tcp-1 para mapear ubicaciones de genes.
- Se analizaron los patrones de expresión génica (alelos maternos vs. paternos) en embriones en desarrollo.
Principales resultados:
- El locus Tme se localizó en una región de 800-1,100 kb.
- Los genes del receptor del factor de crecimiento similar a la insulina tipo 2 (Igf2r) y de la superóxido mitocondrial dismutasa-2 (Sod-2) estaban ausentes tanto en los mutantes de deleción de Thp como en los de tLub2.
- Igf2r exhibió una expresión materna específica, lo que indica que está impresa, mientras que Tcp-1, Plg y Sod-2 mostraron una expresión bialélica.
Conclusiones:
- El gen del receptor del factor de crecimiento similar a la insulina tipo 2 (Igf2r) está impreso y ubicado muy cerca de, o es idéntico a, el locus Tme.
- Este hallazgo proporciona el primer gen impreso clonado asociado con una conocida mutación de efecto maternal en ratones.
- Comprender la impresión de Igf2r ofrece información crucial sobre los mecanismos de letalidad embrionaria asociada a Tme y los procesos de impresión genómica más amplios.
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