Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility

H. M. Hsieh-Li, D. P. Witte, M. Weinstein, W. Branford, H. Li, K. Small, S. S. Potter

Research output: Contribution to journalArticle

345 Citations (Scopus)

Abstract

Hoxa 11 is a murine Abdominal-B-type homeobox gene. The structure of this gene is presented, including genomic and cDNA sequence. The cDNA includes the complete open reading frame and based on primer extension results is near full length. Surprisingly, the antisense strand of Hoxa 11 was found to be transcribed. Moreover, these antisense transcripts were processed and polyadenylated. The developmental expression patterns for both sense and antisense transcripts were examined using serial section and whole-mount in situ hybridizations. Hoxa 11 transcription patterns were defined in the limbs, kidney and stromal cells surrounding the Mullerian and Wolffian ducts. Of particular interest, in the developing limbs, the sense and antisense transcripts showed complementary 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 female sterility. The female mutants produce normal ova, which develop properly post-fertilization when transferred to wild-type surrogate mothers. The Hoxa 11 homozygous mutants are shown to provide a defective uterine environment. The mutant males exhibited a malformation of the vas deferens that resembles a partial homeotic transformation to an epididymis. In addition, the mutant testes fail to descend properly into the scrotum and, likely as a result, spermatogenesis is perturbed.

Original languageEnglish
Pages (from-to)1373-1385
Number of pages13
JournalDevelopment
Volume121
Issue number5
Publication statusPublished - 1995

Keywords

  • Antisense transcripts
  • Homeobox gene
  • Limb development
  • Mouse
  • Spermatogenesis
  • Uterus

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility'. Together they form a unique fingerprint.

Cite this