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.

Towards Characterisation of a C. elegans Huntingtin Interacting Protein

J. Alex Parker, Ann M. Rose

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
        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.