Disease relevance of Tcd1a

• One deletion, T(30H), together with three others, T(31H), T(33H), and T(36H), which extended more proximally, caused male sterility when heterozygous with a complete t haplotype and also enhanced transmission ratio of the partial t haplotype t(6), and this was attributed to deletion of the Tcd1 locus [1].
• We find that the distorter activity of Tcd1 is distinct from a linked sterility factor, originally called tcs1 [2].

High impact information on Tcd1a

• Tagap1 maps to the Tcd1 interval and has four t loci, which encode altered proteins including a C-terminally truncated form [3].
• Combined with the recent identification of another putative t complex distorter, Tctex2, within the outer dynein arm, these results support the hypothesis that transmission ratio distortion (meiotic drive) of mouse t haplotypes involves dysfunction of both flagellar inner and outer dynein arms but does not require the cytoplasmic isozyme [4].
• In this, study a transgenic approach was used to identify the proximal sterility locus, tcs1 (S1), and test its role in TRD [5].
• The mouse t complex distorter/sterility candidate, Dnahc8, expresses a gamma-type axonemal dynein heavy chain isoform confined to the principal piece of the sperm tail [6].
• Heterozygosity for a t haplotype (t) in male mice results in distorted transmission (TRD) of the t-bearing chromosome 17 homolog to their offspring [6].

Biological context of Tcd1a

• One factor, Tcd1, was previously shown to be amorphic using a chromosome deletion [2].
• Sperm carrying the responder locus (Tcr) have a high probability of fertilizing eggs at the expense of wild-type sperm, provided that distorter loci (Tcd-1 to Tcd-5) are expressed during spermatogenesis [7].
• This analysis shows that segmental exchange, either by gene conversion or double crossing-over, has occurred at molecular markers in the vicinity of a gene, Dnahc8, that is a candidate for the t complex distorter locus Tcd2 [8].
• The Ca(2+)-dependent sperm tail curvature phenotypes, "fishhook", where abnormally high levels of sperm exhibit sharp bends in the midpiece, and "curlicue", where motile sperm exhibit a chronic negative curving of the entire tail, have been tightly linked to t-associated male TRD and sterility traits, respectively [6].
• RESULTS: The Tg8 line of transgene carriers had a significant (P < 0.001) TRD, due to reduced fertilizing ability of transgene-bearing sperm [9].

Anatomical context of Tcd1a

• Genomic structure around joining segments and constant regions of swine T-cell receptor alpha/delta (TRA/TRD) locus [10].
• In these animals, V(D)J rearrangements are detected in thymus, lymph nodes, and spleen at the TRB locus, and in thymus and lymph nodes at the TRD locus [11].
• Our earlier studies on carriers of spontaneous mutations of mouse Sperm Adhesion Molecule 1 (Spam1) suggested that TRD results from biochemically different sperm, due to a lack of transcript sharing through the intercellular cytoplasmic bridges of spermatids [9].

Other interactions of Tcd1a

• To overcome limitations imposed by recombination suppression, we used a series of deletions within the t complex in trans to t chromosomes to characterize the Tcd1 region [2].
• It is suggested that the original distorter Tcd1 in fact consists of two loci: Tcd1a, lying between D17Mit164 and D17Leh48, and Tcd1b, lying between T and D17Leh66E [1].
• An allele of the mouse brachyury locus, T22H, had been shown previously to involve a deletion of several markers in the proximal part of chromosome 17, and almost certainly includes deletion of the t-complex distorter gene Tcd-1 [12].
• YACs mapped with respect to deletion breakpoints localize tcs1 to a 1.1-Mb interval flanked by D17Aus9 and Tctex1 [2].
• The possibility that the Sod-2 locus is related to some of the t-complex distorter or responder loci is discussed [13].

Analytical, diagnostic and therapeutic context of Tcd1a

• METHODS: Carriers of Spam1-Hyal5 BAC transgenes were mated with wild-type female mice and the progeny analyzed for TRD by PCR genotyping [9].

References