The mouse vibrator mutation causes an early-onset progressive action tremor, degeneration of brain stem and spinal cord neurons, and juvenile death. We cloned the vibrator mutation using an in vivo positional complementation approach and complete resequencing of the resulting 76 kb critical region from vibrator and its parental chromosome. The mutation is an intracisternal A particle retroposon insertion in intron 4 of the phosphatidylinositol transfer protein alpha gene, causing a 5-fold reduction in RNA and protein levels. Expression of neurofilament light chain is also reduced in vibrator, suggesting one signaling pathway that may underlie vibrator pathology. The vibrator phenotype is suppressed in one intercross. We performed a complete genome scan and mapped a major suppressor locus (Mvb-1) to proximal chromosome 19.

Stipulating to be bound by an earlier claim construction decision has many advantages: it streamlines the case, saves time and money on litigation costs, and allows parties to focus their arguments on real areas of disagreement. However, sometimes parties that are looking for clarity will stipulate to an earlier claim construction, only to discover that an unforeseen consequence of that construction is fatal to their case. One pharmaceutical company learned this lesson the hard way, when it stipulated to be bound by a construction rendered in an earlier case involving a different defendant. The Federal Circuit ruled that the earlier construction had implications for a term not explicitly construed in the earlier case, thus defeating a noninfringement argument predicated on a new construction for that term.