A detailed analysis of these mice is ongoing. These activities are mediated by the Met receptor protein-tyrosine kinase. Mutations of both tyrosine residues to phenyl-alanine essentially mimicked the phenotype previously reported for the null mutation, including embryonic lethality and lack of migratory muscle cells. This demonstrated that these two tyrosine residues are both necessary, and possibly sufficient for Met receptor signaling. We next mutated one of the two docking sites in such a way that the effector Grb2 was no longer able to bind to Met and thereby caused a dramatic reduction in HGF-induced Ras activation.
Homozygous mutants show severe deficits in certain aspects of learning and memory.
Ras-GRF mutants do not learn to fear and avoid aversive stimuli in classical Pavlovian tasks that require the function of the amygdala. In contrast, Ras-GRF mutants behave normally in spatial learning tasks like the Morris water maze, a test known to require hippocampal function. In 1996, the EMBL Transgenic Core Facility, headed by Anne Plueck-Becklas, generated a number of new knockout and transgenic mouse lines for groups in Cell regulation and Gene expression Programs. In addition, new techniques were established, including the generation of germline chimeras by the morula aggregation technique and long-term embryo freezing. Timing of neuronal death in trkA, trkB, trkC mutant embryos reveals developmental changes in sensory neuron dependence on Trk signalling.