Reversion in expression of hypoxanthine guanine phosphoribosyl transferase following cell hybridization

Hybridization of mutant cell lines deficient in hypoxanthine guanine phosphoribosyl transferase (HGPRT; EC 2.4.2.8) from a variety of established rodent sources with HGPRT⁺ human cells yielded progeny cells which grew in selective medium containing hypoxanthine, aminopterin and thymidine (HAT). The same result was obtained when the human cell used was an HGPRT^- transformed line derived from a patient with the Lesch Nyhan syndrome. Electrophoretic analysis indicated that all HAT resistant progeny clones contained an active HGPRT enzyme which was indistinguishable from the wild type enzyme of the corresponding normal rodent cells. In contrast, no HAT resistant cells have been obtained when the same HGPRT^- rodent cells were subjected to fusion processes in the absence of human cells or when they were fused with similarly derived HGPRT^- mutant cells of other rodents. Reversion in expression of the rodent gene for HGPRT was detected in clones which retained one or more human chromosomes and in clones which contained no detectable human chromosomal material. The observed reexpression of rodent HGPRT in HAT resistant clones suggests that HGPRT⁺ as well as HGPRT^- human cells contributed a factor which determined the expression of respective rodent structural genes for HGPRT. In contrast, HGPRT^- rodent cells were unable to induce the synthesis of normal HGPRT in the cells derived from the patient with the Lesch Nyhan syndrome.