Worm Breeder's Gazette 15(2): 44 (February 1, 1998)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Department of Medical Genetics,University of British Columbia, Vancouver, B.C., V6T 1Z3, Canada
We are interested in determining the function of the putative C. elegans gene product ZK370.3, which shares sequence identity with human HIP1 (Huntingtin Interacting Protein 1), and Sla2p (Synthetic Lethal with Actin Binding Protein 1) of yeast. ZK370.3 is of particular interest, as its human counterpart is known to interact specifically with the human huntingtin protein. Human huntingtin contains a polymorphic CAG repeat (coding for glutamine) in its first exon, which is responsible for the disease Huntington's chorea. Normal individuals possess between 10-34 repeats, whereas affected individuals typically have more than 36 CAG repeats. It is largely unknown as to how the expanded repeat manifests as disease. One theory suggests that specific subsets of proteins are unable to interact with the mutant huntingtin, which may contribute to the disease phenotype. A screen to identify proteins that interact with human huntingtin identified a protein (HIP1) whose interaction was affected by the size of the glutamine repeat (Kalchman et al. 1997, Wanker et al. 1997). The larger the repeat, the weaker the interaction between huntingtin and HIP1. In collaboration with the Michael Hayden laboratory at the University of British Columbia, we are working to determine if ZK370.3 can interact with human huntingtin. We are currently characterising the gene structure of ZK370.3. Through RT-PCR with the 5' primer containing either the SL1 or SL2 sequence, and the 3' primer being specific to ZK370.3, we have determined that the gene is trans spliced to SL1. With this information, we are employing several strategies to determine the expression pattern of ZK370.3. We are in the process of isolating and characterising deletion mutants corresponding to ZK370.3. Using the protocol described by Moulder and Barstead (http://snmc01.omrf.uokhsc.edu/revgen/RevGen.html), we have screened our UV-TMP library. We are currently characterising a deletion that removes a large portion of ZK370.3. It is hoped that by studying the C. elegans HIP1 counterpart, we may be able to determine its function not only in the nematode, but perhaps its contribution to the disease state in humans.