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In a mouse mutagenesis screen, we isolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that Myk/+ mice carry a mutation (I810N) which renders the normally expressed [Na.sup.+],[K.sup.+]-ATPase [alpha]3 isoform inactive. Total [Na.sup.+],[K.sup.+]-ATPase activity was reduced by 42% in Myk/+ brain. The epilepsy in Myk/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type [Na.sup.+],[K.sub.+]-ATPase [alpha]3 by transgenesis, which also rescued [Na.sup.+],[K.sup.+]-ATPase activity. Our findings reveal the functional significance of the [Na.sup.+],[K.sup.+]-ATPase [alpha]3 isoform in the control of epileptiform activity and seizure behavior. alpha3 [Na.sup.+],[K.sup.+] ATPase | BAC rescue | epilepsy | forward genetic screen | mouse

Research has been conducted on EphB/EphrinB receptors. Results indicate that beta-catenin and TCF control the expression of these receptors and their ligand ephrin-B1 in colorectal cancer.

The apoptosis of cells is necessary during development to establish normal organ size and architecture. The caspase cascade is an important component of the cell death machinery. Investigations of the requirement of various mammalian cells for two components of these cascade, caspase 9 (Casp9) and caspase 3 (Casp3) revealed that there are four cellular death pathways wherein the requirements for Casp9 and Casp3 differ.

Two mutations in the mouse germline were generated to address the biological functions of the Eph family member Nuk. The two mutations are a protein null allele (Nuk1) and an allele that encodes a Nuk-beta gal fusion receptor whose tyrone kinase and C-terminal domains are absent. Most axons forming the anterior commissure's posterior tract aberrantly migrate to the brain's floor in Nuk1 homozygous brains. This prevents cortical neurons from linking the two temporal lobes. Results demonstrate the role of Nuk in pathfinding specific axons in the mammalian central nervous system.