title: The T complex distorter 2 candidate gene, Dnahc8, encodes at least two testis-specific axonemal dynein heavy chains that differ extensively at their amino and carboxyl termini.
abstract: Homozygosity for the t haplotype allele of the testis-specifically expressed axonemal dynein heavy chain (axDHC) gene, Dnahc8, has been linked to male sterility resulting from aberrant sperm motility. However, the near absence of Dnahc8 expression has been associated with male sterility resulting from an early breakdown in sperm flagellar development. Although axDHCs are integral participants in flagellar motility, a role in flagellar morphogenesis has never been attributed to a member of this highly conserved gene family. To gain a better understanding of this presumed novel role for Dnahc8, we have studied the organization and expression of full-length Dnahc8(+) and Dnahc8(t) transcripts. Our results demonstrate the existence of at least two alternatively spliced, testis-specific Dnahc8 mRNAs transcribed from both the + and t alleles. A highly expressed isoform encodes a protein with significant homology nearly throughout to the gamma heavy chain of the Chlamydomonas axonemal outer arm dynein, while a more poorly expressed isoform codes for a protein whose sequence diverges significantly from that of other axDHCs at both its N and C termini. While in situ hybridization studies demonstrate that both mRNA species accumulate exclusively in mid to late spermatocytes, each isoform shows spatial independence. Additional experiments demonstrate the existence of a testis-expressed mRNA with no significant open reading frame, a portion of which is antisense to the 5'-untranslated region of the highly divergent Dnahc8 isoform. The cumulative data imply that Dnahc8 may have acquired functional plasticity in the testis through the tightly controlled expression of both typical and unusual isoforms.
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, 19140, USA.
authors.forename: Sadhana A
authors.initials: SA
authors.lastname: Samant
authors.forename: Olugbemiga
authors.initials: O
authors.lastname: Ogunkua
authors.forename: Ling
authors.initials: L
authors.lastname: Hui
authors.forename: John
authors.initials: J
authors.lastname: Fossella
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Pilder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D056444:Axonemal Dyneins; D001483:Base Sequence; D001665:Binding Sites; D018076:DNA, Complementary; D004398:Dyneins / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017421:Sequence Analysis; D012689:Sequence Homology, Nucleic Acid; D013737:Testis / Q000201:enzymology*
chemical_list: D018076:DNA, Complementary; C467322:Dnah8 protein, mouse; D007527:Isoenzymes; D056444:Axonemal Dyneins; D004398:Dyneins