The him (high incidence of males) mutations increase the frequency of chromosome nondisjunction, and are therefore predicted to identify gene products important to meiosis and/or mitosis. The
him-10 (
e1511ts) mutation results in ~20% male self-progeny at 20oC and sterility at 25oC. Previous characterization of this mutation suggests that the
him-10 gene product functions in mitotic chromosome segregation in the germline and soma. First, cytological observation of developing oocytes suggests that the Him and sterile phenotypes are caused in part by gamete aneuploidy due to defective germline mitosis (1). Second, a four-to six-fold increase in free duplication loss occurs in the somatic cells of
him-10 mutants(2). Our data on the temperature-sensitive period of
e1511ts suggest that both meiotic and mitotic divisions are affected by the mutation. Specifically,
him-10 hermaphrodites cultured at 25oC during L4 are less fecund than siblings raised continuously at 20o. This reduction in fertility is partially rescued by mating with N2 males. Taken together these data suggest that meiotic divisions of hermaphrodite sperm during L4 require wild-type
him-10 function. Based on the phenotypic defects of
him-10 (
e1511ts), the wild-types gene product functions in at least three distinct type of divisions: hermaphrodite germline mitosis, embryonic mitosis, and hermaphrodite sperm meiosis. In order to more completely understand the function of
him-10 we cloned the gene and attempted to characterize the null phenotype. Partial rescue of the temperature-sensitive sterile phenotype implicated two ORFs on the W03A3 cosmid as candidates for
him-10. Identification of a proline to serine missense mutation in the R12b2.4 ORF of
e1511ts animals confirmed that
him-10 encodes a novel 491 amino acid protein. Based on the genetic and molecular data, it is unlikely that
e1511ts is a null mutation. Moreover, several attempts to generate a deletion of the locus have failed. Therefore, we conducted dsRNA interference experiments to identify the null phenotype. Injection of dsR12b2.4 causes embryonic lethality in most self-progeny of injected hermaphrodites. Animals that escape embryonic lethality can arrest as larva or develop into Unc or sterile Unc hermaphrodites. The embryonic lethality may be caused by disruption of germline divisions in the injected animals or by defective embryonic mitosis in the progeny. The adult escapers were Unc hermaphrodites suggesting that somatic rather than germline divisions were affected by RNAi. A defect in germline divisions should have resulted in male self-progeny. Identification of a null allele will help to clarify whether the primary function of
him-10 is somatic, germline, or both. At present the combined data suggest that
him-10 encodes a novel general segregation factor. 1. Villeneuve, A.M. (1994) A C. elegans mitotic mutant WBG 12.4:58 2. Hedgecock, E.M. and Herman, R.K. (1995) The
ncl-1 gene and genetic mosaics of Caenorhabditis elegans. Genetics 141: 989-1006.