HOXA-11 STRUCTURE, EXTENSIVE ANTISENSE TRANSCRIPTION, AND FUNCTION INMALE AND FEMALE FERTILITY

Hoxa 11 is a murine Abdominal-B-type homeobox gene. The structure of t his gene is presented, including genomic and CDNA sequence. The cDNA i ncludes the complete open reading frame and based on primer extension results is near full length. Surprisingly, the antisense strand of Hox a 11 was found to be transcribed. Moreover, these antisense transcript s were processed and polyadenylated. The developmental expression patt erns for both sense and antisense transcripts were examined using seri al section and wholemount in situ hybridizations. Hoxa 11 transcriptio n patterns were defined in the limbs, kidney and stromal cells surroun ding the Mullerian and Wolffian ducts. Of particular interest, in the developing limbs, the sense and antisense transcripts showed complemen tary expression patterns, with antisense RNAs increasing in abundance in regions where sense RNAs were diminishing in abundance. Furthermore , targeted mutation of Hoxa 11 is shown to result in both male and fem ale sterility. The female mutants produce normal ova, which develop pr operly postfertilization when transferred to wild-type surrogate mothe rs. The Hoxa 11 homozygous mutants are shown to provide a defective ut erine environment. The mutant males exhibited a malformation of the va s deferens that resembles a partial homeotic transformation to an epid idymis. In addition, the mutant testes fail to descend properly into t he scrotum and, likely as a result, spermatogenesis is perturbed.