[P2.40]: Gender specific transmission across generations of behavioral effects induced by maternal exposure to moderate doses of corticosterone during lactation

used transgenic mice expressing activated human Val12 Ha-Ras selectively in neurons resulting in enhanced cortical synaptic longterm potentiation (Heumann et al, 2000; Arendt et al., 2004). The crossbreeding of heterozygous MeCP2+/−-females with transgenic synRas-males resulted in a dramatically increased lethality. Furthermore, in contrast to heterozygous MeCP−/y-males double transgenic synRas/MeCP−/y-males did not survive beyond postnatal day 28. Female synRas/MeCP2+/−-mice had an almost normal lifespan. However, these double transgenic female mice developed an enhanced anxiety-like behaviour in the elevated plus maze comparable to that of the strongly affected MeCP2−/y-males. We conclude that activation of the Ras/MAPkinase pathway in neurons accelerated the adverse RTT phenotype and therefore Ras may serve as a target for therapeutical intervention. References: