Graduate Student Directory
|Degree Program:||Molecular, Cellular, and Developmental Biology||Email:||firstname.lastname@example.org|
|Major Professor:||Deanna Smith|
Lis1 haploinsufficiency in humans results in a “smooth brain” phenotype called lissencephaly, and also causes severe cognitive and motor impairments and epilepsy. Various mouse models have been used to examine the role of Lis1 during brain development, and it is clear that Lis1 regulates a microtubule motor, cytoplasmic dynein. Intriguingly, Lis1 expression remains high in adult brains indicating that it plays a role in mature systems. Indeed, our group found that Lis1 and several related proteins regulate dynein-dependent axon transport in cultured adult rat sensory neurons. I am interested in examining Lis1 function in the adult mouse, and in order to bypass the embryonic impact of Lis1 loss I have utilized a tamoxifen inducible Cre-mediated recombination system to knock out Lis1 in adult mice (8 weeks). I chose to cross floxed Lis1 mice with mice in which Cre expression is driven by an actin promoter. I find that loss of Lis1 in adult mice causes severe behavioral abnormalities and death. These phenotypes are not observed in any of a variety of control animals. Thus, Lis1 plays a crucial role in an adult mammalian system. I am now in the process of determining the cellular and molecular causes of these major defects.