Dramatic, expansion-biased, age-dependent, tissue-specific somatic mosaicism in a transgenic mouse model of triplet repeat instability

Human Molecular Genetics

Volumn 9, Issue 3, 2000, Pages 439-445

  Fortune, M Teresa ^a   Vassilopoulos, Christos ^a,c   Coolbaugh, Mary I ^b   Siciliano, Michael J ^b   Monckton, Darren G ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c NONE   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

REPETITIVE DNA; TRINUCLEOTIDE;

AGE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; GENE MUTATION; GERM LINE; HEREDITY; KIDNEY; MOSAICISM; MOUSE; MYOTONIC DYSTROPHY; NONHUMAN; PRIORITY JOURNAL; SYMPTOM; TISSUE SPECIFICITY; TRANSGENIC MOUSE; TRINUCLEOTIDE REPEAT;

EID: 0034639711     PISSN: 09646906     EISSN: None     Source Type: Journal    
DOI: 10.1093/hmg/9.3.439     Document Type: Article

References (48)

1. Wells, R.D. and Warren, S.T. (1998) Genetic Instabilities and Hereditary Neurological Diseases. Academic Press, London, UK, 829 pp.
2. Knob, M.D., Moseley, M.L., Schut, L.J., Benzow, K.A., Bird, T.D., Day, J.W. and Ranum, L.P. (1999) An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nature Genet., 21, 379-384.
3. Richards, R.I. and Sutherland, G.R. (1992) Dynamic mutations: a new class of mutations causing human disease. Cell, 70, 709-713.
4. Fu, Y.H., Pizzuti, A., Fenwick, R.G., King, J., Rajnarayan, S., Dunne, P.W., Dubel, J., Nasser, G.A., Ashizawa, T., de Jong, P. et al. (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science, 255, 1256-1258.
5. Brook, J.D., McCurrach, M.E., Harley, H.G., Buckler, A.J., Church, D., Aburatani, H., Hunter, K., Stanton, V.P., Thirion, J.-P., Hudson, T. et al. (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell, 68, 799-808.
6. Mahadevan, M., Tsilfidis, C., Sabourin, L., Shutler, G., Amemiya, C., Jansen, G., Neville, C., Narang, M., Barcelo, J., O'Hoy, K. et al. (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science, 255, 1253-1255.
7. Boucher, C.A., King, S.K., Carey, N., Krahe, R., Winchester, C.L., Rahman, S., Creavin, T., Meghji, P., Bailey, M.E.S., Chartier, F.L. et al. (1995) A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat. Hum. Mol. Genet., 4, 1919-1925.
8. Otten, A.D. and Tapscott, S.J. (1995) Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. Proc. Natl Acad. Sci. USA, 92, 5465-5469.
9. Klesert, T.R., Otten, A.D., Bird, T.D. and Tapscott, S.J. (1997) Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP. Nature Genet., 16, 402-406.
10. Harper, P.S., Harley, H.G., Reardon, W. and Shaw, D.J. (1992) Anticipation in myotonic dystrophy: new light on an old problem. Am. J. Hum. Genet., 51, 10-16.
11. Wong, L.-J.C, Ashizawa, T., Monckton, D.G., Caskey, C.T. and Richards, C.S. (1995) Somatic heterogeneity of the CTG repeat in myotonic dystrophy is age and size dependent. Am. J. Hum. Genet., 56, 114-122.
12. Martorell, L., Monckton, D.G., Gamez, J., Johnson, K.J., Gich, I., Lopez de Munain, A. and Baiget, M. (1998) Progression of somatic CTG repeat length heterogeneity in the blood cells of myotonic dystrophy patients. Hum. Mol. Genet., 7, 307-312.
13. Monckton, D.G., Wong, L.-J.C., Ashizawa, T. and Caskey, C.T. (1995) Somatic mosaicism, germline expansions, germline reversions and intergenerational reductions in myotonic dystrophy males: small pool PCR analyses. Hum. Mol. Genet., 4, 1-8.
14. Anvret, M., Ahlberg, G., Grandell, U., Hedberg, B., Johnson, K. and Edstrom, L. (1993) Larger expansions of the CTG repeat in muscle compared to lymphocytes from patients with myotonic dystrophy. Hum. Mol. Genet., 2, 1397-1400.
15. Ashizawa, T., Dubel, J.R. and Harati, Y. (1993) Somatic instability of CTG repeat in myotonic dystrophy. Neurology, 43, 2674-2678.
16. Thornton, C.A., Johnson, K.J. and Moxley, R.T. (1994) Myotonic dystrophy patients have larger CTG expansions in skeletal muscle than in leukocytes. Ann. Neurol., 35, 104-107.
17. Lavedan, C., Hofmann-Radvanyi, H., Shelbourne, P., Rabes, J.-P., Duros, C., Savoy, D., Dehaupas, I., Luce, S., Johnson, K. and Junien, C. (1993) Myotonic dystrophy: size-and sex-dependent dynamics of CTG meiotic instability, and somatic mosaicism. Am. J Hum. Genet., 52, 875-883.
18. Jansen, G., Willems, P., Coerwinkel, M., Nillesen, W., Smeets, H., Vits, L., Howeler, C., Brunner, H. and Wieringa, B. (1994) Gonosomal mosaicism in myotonic dystrophy patients: involvement of mitotic events in (CTG)n variation and selection against extreme expansion in sperm. Am. J. Hum. Genet., 54, 575-585.
19. Wöhrle, D., Kennerknecht, I., Wolf, M., Enders, H., Schwemmle, S. and Steinbach, P. (1995) Heterogeneity of DM kinase repeat expansion in different fetal tissues and further expansion during cell proliferation in vitro: evidence for a causal involvement of methyl-directed DNA mismatch repair in triplet repeat stability. Hum. Mol. Genet., 4, 1147-1153.
20. Wong, L.J. and Ashizawa, T. (1997) Instability of the (CTG)n repeat in congenital myotonic dystrophy. Am. J. Hum. Genet., 61, 1445-1448.
21. Tachi, N., Ohya, K., Chiba, S. and Sato, T. (1993) Unstable DNA in a patient with a severe form of congenital myotonic dystrophy. J. Neurol. Sci., 119, 180-182.
22. Tachi, N., Ohya, K., Chiba, S., Sato, T. and Kikuchi, K. (1995) Minimal somatic instability of CTG repeat in congenital myotonic dystrophy. Pediatr. Neurol., 12, 81-83.
23. Joseph, J.T., Richards, C.S., Anthony, D.C., Upton, M., Perez-Atayde, A.R. and Greenstein, P. (1997) Congenital myotonic dystrophy pathology and somatic mosaicism. Neurology, 49, 1457-1460.
24. Bingham, P.M., Scott, M.O., Wang, S., McPhaul, M.J., Wilson, E.M., Garben, J.Y., Merry, D.E. and Fischbeck, K.H. (1995) Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice. Nature Genet., 9, 191-196.
25. Burright, E.N., Clark, H.B., Servadio, A., Matilla, T., Feddersen, R.M., Yunis, W.S., Duvick, L.A., Zoghbi, H.Y. and Orr, H.T. (1995) SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell. 82, 937-948.
26. Goldberg, Y.P., Kalchman, M.A., Metzler, M., Nasir, J., Zeisler, J., Graham, R., Koide, H.B., O'Kusky, J., Sharp, A.H., Ross, C.A. et al. (1996) Absence of disease phenotype and intergenerational stability of the CAG repeat in transgenic mice expressing the human Huntington disease transcript. Hum. Mol. Genet., 5, 177-185.
27. Monckton, D.G., Coolbaugh, M.I., Ashizawa, K., Siciliano, M.J. and Caskey, C.T. (1997) Hypermutable myotonic dystrophy CTG repeats in transgenic mice. Nature Genet., 15, 193-196.
28. Mangiarini, L., Sathasivam, K., Mahal, A., Mott, R., Seller, M. and Bates, G.P. (1997) Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation. Nature Genet., 15, 197-200.
29. Gourdon, G., Radvanyi, F., Lia, A.S., Duros, C. Blanche, M., Abitbol, M., Junien, C. and Hofmann Radvanyi, H. (1997) Moderate intergenerational and somatic instability of a 55 CTG repeat in transgenic mice. Nature Genet., 15, 190-192.
30. La Spada, A.R., Peterson, K.R., Meadows, S.A., McClain, M.E., Jeng, G., Chmelar, R.S., Haugen, H.A., Chen, K., Singer, M.J., Moore, D. et al. (1998) Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability. Hum. Mol. Genet., 7, 959-967.
31. Sato, T., Oyake, M., Nakamura, K., Nakao, K., Fukusima, Y., Onodera, O., Igarashi, S., Takano, H., Kikugawa, K., Ishida, Y. et al. (1999) Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients. Hum. Mol. Genet., 8, 99-106.
32. Ikeda, H., Yamaguchi, M., Sugai, S., Aze, Y., Narumiya, S. and Kakizuka, A. (1996) Expanded polyglutamine in the Machado-Joseph disease protein induces cell-death in vitro and in vivo. Nature Genet., 13, 196-202.
33. Wheeler, V.C., Auerbach, W., White, J.K., Srinidhi, J., Auerbach, A., Ryan, A., Duyao, M.P., Vrbanac, V., Weaver, M., Gusella, J.F. et al. (1999) Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse. Hum. Mol. Genet., 8, 115-122.
34. Shelbourne, P.F., Killeen, N., Hevner, R.F., Johnston, H.M., Tecott, L., Lewandoski, M., Ennis, M., Ramirez, L., Li, Z., Iannicola, C. et al. (1999) A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum. Mol. Genet., 8, 763-774.
35. Lia, A.S., Seznec, H., Hofmann Radvanyi, H., Radvanyi, F., Duros, C., Saquet, C., Blanche, M., Junien, C. and Gourdon, G. (1998) Somatic instability of the CTG repeat in mice transgenic for the myotonic dystrophy region is age dependent but not correlated to the relative intertissue transcription levels and proliferative capacities. Hum. Mol. Genet., 7, 1285-1291.
36. Jeffreys, A.J., Tamaki, K., MacLeod, A., Monckton, D.G., Neil, D.L. and Armour, J.A.L. (1994) Complex gene conversion events in germline mutation at human minisatellites. Nature Genet., 6, 136-145.
37. Telenius, H., Kremer, B., Goldberg, Y.P., Theilmann, J., Andrew, S.E., Zeisler, J., Adam, S., Greenberg, C., Ives, E.J., Clarke, L.A. et al. (1994) Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nature Genet., 6, 409-414.
38. Chong, S.S., McCall, A.E., Cota, J., Subramony, S.H., Orr, H.T., Hughes, M.R. and Zoghbi, H.Y. (1995) Gametic and somatic tissue specific heterogeneity of the expanded SCA1 CAG repeat in spinocerebellar ataxia type 1. Nature Genet., 10, 344-350.
39. Cancel, G., Gourfinkel-An, I., Stevanin, G., Didierjean,O., Abbas, N., Hirsch, E., Agid, Y. and Brice, A. (1998) Somatic mosaicism of the CAG repeat expansion in spinocerebellar ataxia type 3/Machado-Joseph disease. Hum. Mutat., 11, 23-27.
40. Takano, H., Onodera, O., Takahashi, H., Igarashi, S., Yamada, M., Oyake, M., Ikeuchi, T., Koide, R., Tanaka, H., Iwabuchi, K. et al. (1996) Somatic mosaicism of expanded CAG repeats in brains of patients with dentatorubral-pallidoluysian atrophy: cellular population-dependent dynamics of mitotic instability. Am. J. Hum. Genet., 58, 1212-1222.
41. Ishii, S., Nishio, T., Sunohara, N., Yoshihara, T., Takemura, K., Hikiji, K., Tsujino, S. and Sakuragawa, N. (1996) Small increase in triplet repeat length of cerebellum from patients with myotonic dystrophy. Hum. Genet., 98, 138-140.
42. Bates, G.P. and Davies, S.W. (1997) Transgenic mouse models of neurodegenerative disease caused by CAG/polyglutamine expansions. Mol. Med. Today, 3, 508-515.
43. 3 into male rats and mice. Am J. Anat., 106, 247-265.
44. 3H-thymidine. J. Comp. Neurol., 271, 589-603.
45. Cameron, I.L. (1970) Cell renewal in the organs and tissues of the nongrowing adult mouse. Tex. Rep. Biol. Med., 28, 203-248.
46. Kaytor, M.D., Burright, E.N., Duvick, L.A., Zoghbi, H.Y. and Orr, H.T. (1997) Increased trinucleotide repeat instability with advanced maternal age. Hum. Mol. Genet., 6, 2135-2139.
47. Brock, G.J.R., Anderson, N.H. and Monckton, D.G. (1999) Cis-acting modifiers of expanded CAG/CTG triplet repeat expandability: associations with flanking GC content and proximity to CpG islands. Hum. Mol. Genet., 8, 1061-1067.
48. Gardiner-Garden, M. and Frommer, M. (1987) CpG islands in vertebrate genomes. J. Mol. Biol., 196, 261-282.