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Functional analysis of a t complex responder locus transgene in mice

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Abstract

Transmission ratio distortion (TRD) of mouse t haplotypes occurs through the interaction of multiple distorter loci with the t complex responder (Tcr) locus. Males heterozygous for a t haplotype will transmit the t-bearing chromosome to nearly all of their offspring. This process is mediated by the production of functionally inequivalent gametes: wildtype meiotic partners of t spermatozoa are rendered functionally inactive. The Tcr locus, which is required for TRD to occur, is thought to somehow protect its host spermatid from the sperm-inactivating effects of linked distorter genes (Lyon 1984). In previous work, Tcr was mapped to a small genetic interval in t haplotypes, and a candidate gene from this region was isolated (Tcp-10b t). In this work, we further localize Tcr to a 40-kb region that contains the 21-kb Tcp-10b t gene. A cloned genomic copy of Tcp-10b t was used to generate transgenic mice. The transgene was bred into a variety of genetic backgrounds to test for non-Mendelian segregation. Abberrant segregation was observed in some mice carrying either a complete t haplotype or a combination of certain partial t haplotypes. These observations, coupled with those of Snyder and colleagues (in this issue), provide genetic and functional evidence that the Tcp-10b t gene is Tcr. However, other genotypes that were predicted to produce distortion did not. The unexpected data from a variety of crosses in this work and those of our colleagues suggest that elements to the TRD system and the Tcr locus remain to be identified.

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References

  • Artzt, K., Shin, H.-S., and Bennett, D.: Gene mapping within the T/t complex in the mouse. II. Anomalous position of the H-2 complex in t haplotypes. Cell 28: 471–476, 1982.

    Google Scholar 

  • Bennett, D., Alton, A.K., and Artzt, K.: Genetic analysis of transmission ratio distortion by t-haplotypes in the mouse. Genet Res 41: 29–45, 1983.

    Google Scholar 

  • Bullard, D. and Schimenti, J.: Molecular cloning and genetic mapping of the t complex responder candidate gene family. Genetics 124: 957–966, 1990.

    Google Scholar 

  • Cebra-Thomas, J., Decker, C., Snyder, L., Pilder, S., and Silver, L.: An allele- and haploid specific product generated by alternative splicing from a mouse t complex responder locus candidate. Nature 349: 239–241, 1991.

    Google Scholar 

  • Chomczynski, P. and Sacchi, N.: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159, 1987.

    Google Scholar 

  • Church, G. and Gilbert, W.: Genomic sequencing. Proc Natl Acad Sci USA. 81: 1991–1995, 1984.

    Google Scholar 

  • Committee for Chromosome 17: Maps of mouse Chromosome 17: first report. Mammalian Genome 1: 5–29, 1990.

    Google Scholar 

  • Davies, P. and Willison, K.: Sequence of the t complex Tcp-10a t gene and examination of the Tcp-10 gene family. Mammalian Genome 1: 235–241, 1991.

    Google Scholar 

  • Dunn, L.C., and Bennett, D.: A new case of transmission ratio distortion in the house mouse. Genetics 61: 570–573, 1968.

    Google Scholar 

  • Dunn, L.C. and Bennett, D.: Further studies of a mutation (low) which distorts transmission ratios in the house mouse. Genetics 67: 543–558, 1970.

    Google Scholar 

  • Feinberg, A.P. and Vogelstein, B.: A technique for radiolabelling DNA restriction endonuclease restriction fragments to high specific activity. Anal Biochem 137: 266–267, 1984.

    Google Scholar 

  • Gummere, G.R., McCormick, P.J., and Bennett, D.: The influence of genetic background and the homologous chromosome 17 on t-haplotype transmission ratio distortion in mice. Genetics 114: 235–245, 1986.

    Google Scholar 

  • Hammer, M.F., Bliss, S., and Silver, L.M.: Genetic exchange across a paracentric inversion of the mouse t complex. Genetics 128: 799–812, 1991.

    Google Scholar 

  • Hammer, M.H., Schimenti, J.C., and Silver, L.M.: On the origins of t complex inversions. Proc Natl Acad Sci USA 86: 3261–3265, 1989.

    Google Scholar 

  • Hammerberg, C.: The effects of the t complex upon male reproduction are due to complex genetic interactions between its several regions. Genet Res 39: 219–226, 1982.

    Google Scholar 

  • Herrmann, B., Bucan, M., Mains, P.E., Frischauf, A.-M., Silver, L.M., and Lehrach, H.: Genetic analysis of the proximal portion of the mouse t complex: evidence for a second inversion within t haplotypes. Cell 44: 469–476, 1986.

    Google Scholar 

  • Hogan, B., Constantini, F., and Lacy, E.: Manipulating the Mouse Embryo, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986.

    Google Scholar 

  • Lyon, M.F.: Transmission ratio distortion in mouse t haplotypes is due to multiple distorter genes acting on a responder locus. Cell 37: 621–628, 1984.

    Google Scholar 

  • Lyon, M.F.: Male sterility of the mouse t-complex is due to homozygosity of the distorter genes. Cell 44: 357–363, 1986.

    Google Scholar 

  • Lyon, M.F.: Search for differences among t haplotypes in distorter and responder genes. Genet Res 55: 13–19, 1990.

    Google Scholar 

  • Lyon, M.F.: Deletion of mouse t-complex-distorter-1 produces an effect like that of the t-form of the distorter. Genet Res 59: 27–33, 1992.

    Google Scholar 

  • Lyon, M.F. and Zenthon, J.: Differences in or near the responder region of complete and mouse partial t haplotypes. Genet Res 50: 29–34, 1987.

    Google Scholar 

  • Murti, J.R., Bumbulis, M., and Schimenti, J.: High frequency germline gene conversion in transgenic mice. Mol Cell Biol, in press, 1992.

  • Nadeau, J.H., Varnum, D., and Burkart, D.: Genetic evidence for two t complex tail interraction loci (tct) in t haplotypes. Genetics 122: 895–903, 1989.

    Google Scholar 

  • Pilder, S., Decker, C., Islam, S., Buck, C., Cebra-Thomas, J., and Silver, L.: Concerted evolution of the mouse Tcp-10 gene family: implications for the functional basis of t haplotype transmission ratio distortion. Genomics 12: 35–41, 1991.

    Google Scholar 

  • Rosen, L., Bullard, D., Silver, L., and Schimenti, J.: Molecular cloning of the t complex responder genetic locus. Genomics 8: 134–140, 1990.

    Google Scholar 

  • Schimenti, J.: High throughput mouse DNA isolation for southern blot progeny analysis. Mouse Genome 89: 573, 1991.

    Google Scholar 

  • Schimenti, J. and Hammer, M.: Rapid identification of mouse t haplotypes by PCR polymorphism (PCRP). Mouse Genome 87: 108, 1990.

    Google Scholar 

  • Schimenti, J., Vold, L., Socolow, D., and Silver, L.M.: An unstable family of large DNA elements in the center of mouse t haplotypes. J Mol Biol 194: 583–594, 1987.

    Google Scholar 

  • Schimenti, J.C., Cebra-Thomas, J., Decker, C.L., Islam, S.D., Pilder, S.H., and Silver, L.M.: A candidate gene family for the mouse t complex responder (Tcr) locus responsible for haploid effects on sperm function. Cell 55: 71–78, 1988.

    Google Scholar 

  • Silver, L.M.: Gene dosage effect on transmission ratio distortion and fertility in mice that carry t haplotypes. Genet Res 54: 221–225, 1989.

    Google Scholar 

  • Silver, L.M. and Remis, D.: Five of the nine genetically defined regions of mouse t haplotypes are involved in transmission ratio distortion. Genet Res 49: 51–56, 1987.

    Google Scholar 

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Bullard, D.C., Ticknor, C. & Schimenti, J.C. Functional analysis of a t complex responder locus transgene in mice. Mammalian Genome 3, 579–587 (1992). https://doi.org/10.1007/BF00350625

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