Gene Cloned by Life Sciences Division Scientists (January 1999)

ORNL's Life Sciences Division researchers in the laboratories of E. M. Rinchik and D. K. Johnson, in collaboration with L. J. Stubbs of Lawrence Livermore National Laboratory and R. D. Nicholls of Case Western Reserve University, have cloned a gene in mice that encodes the largest protein described to date. Chemical mutagenesis efforts at ORNL have resulted in eight different point mutations within this giant protein; mutations in this gene lead to variably severe neuromuscular abnormalities, sperm defects, female semi-sterility, and a reduced lifespan with juvenile death. Graduate students M. W. Walkowicz at ORNL and Y. Ji at Case Western isolated and characterized the mouse gene, named Herc2, and later the homologous human gene, HERC2; the protein products are 95% identical in mice and humans. Both genes appear to encode a factor involved in the trafficking and degradation pathways for other proteins in the cell, and are widely expressed in all mouse and human tissues tested. There appear to be related genes in birds, fruit flies, and fish, confirming that the function of this protein has probably been conserved through eons of evolution.

Identification of the human disease equivalent of the abnormalities seen in mice, and of the specific functions of the proteins, will illuminate the common role that protein trafficking and degradation play in neuromuscular function, gametogenesis, and cell development. (Contact: Dabney Johnson, johnsondk@ornl.gov, 865-574-0953; Funding Source: KP)