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PMID: 9671732 Published · ppublish English Journal Article

Telomere length regulation in mice is linked to a novel chromosome locus.

Zhu L, Hathcock KS, Hande P, Lansdorp PM, Seldin MF, Hodes RJ

Abstract

Little is known about the mechanisms that regulate species-specific telomere length, particularly in mammalian species. The genetic regulation of telomere length was therefore investigated by using two inter-fertile species of mice, which differ in their telomere length. Mus musculus (telomere length >25 kb) and Mus spretus (telomere length 5-15 kb) were used to generate F1 crosses and reciprocal backcrosses, which were then analyzed for regulation of telomere length. This analysis indicated that a dominant and trans-acting mechanism exists capable of extensive elongation of telomeres in somatic cells after fusion of parental germline cells with discrepant telomere lengths. A genome wide screen of interspecific crosses, using M. spretus as the recurrent parent, identified a 5-centimorgan region on distal chromosome 2 that predominantly controls the observed species-specific telomere length regulation. This locus is distinct from candidate genes encoding known telomere-binding proteins or telomerase components. These results demonstrate that an unidentified gene(s) mapped to distal chromosome 2 regulates telomere length in the mouse.

MeSH Terms
Animals Chi-Square Distribution Chromosome Mapping Crosses, Genetic Genetic Linkage Mice Mice, Inbred BALB C Mice, Inbred C3H Polymorphism, Genetic Polymorphism, Restriction Fragment Length Telomere
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zhu L
Rowe Program in Genetics, Departments of Biological Chemistry and Medicine University of California, Davis, Davis, CA 95616, USA.
Hathcock K S
Hande P
Lansdorp P M
Seldin M F
Hodes R J
References (32)
32 references, click to expand
  1. Extensive telomere repeat arrays in mouse are hypervariable.
    Nucleic Acids Res. 1990 Dec 11;18(23):6881-8 PMID: 2175882
  2. Short telomeres on human chromosome 17p.
    Nat Genet. 1998 Jan;18(1):76-80 PMID: 9425906
  3. Telomerases.
    Annu Rev Biochem. 1992;61:113-29 PMID: 1497307
  4. Pinning down loose ends: mapping telomeres and factors affecting their length.
    Plant Cell. 1992 Aug;4(8):953-60 PMID: 1356536
  5. Telomere length predicts replicative capacity of human fibroblasts.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114-8 PMID: 1438199
  6. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes.
    Am J Hum Genet. 1993 Apr;52(4):661-7 PMID: 8460632
  7. An alternative pathway for yeast telomere maintenance rescues est1- senescence.
    Cell. 1993 Apr 23;73(2):347-60 PMID: 8477448
  8. Mammalian telomere dynamics: healing, fragmentation shortening and stabilization.
    Curr Opin Genet Dev. 1994 Apr;4(2):203-11 PMID: 8032197
  9. Genetic dissection of complex traits.
    Science. 1994 Sep 30;265(5181):2037-48 PMID: 8091226
  10. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9857-60 PMID: 7937905
  11. Telomeres and telomerase in aging and cancer.
    Curr Opin Genet Dev. 1995 Apr;5(2):249-55 PMID: 7613096
  12. Functional characterization and developmental regulation of mouse telomerase RNA.
    Science. 1995 Sep 1;269(5228):1267-70 PMID: 7544492
  13. Human naive and memory T lymphocytes differ in telomeric length and replicative potential.
    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11091-4 PMID: 7479943
  14. Telomere length and replicative aging in human vascular tissues.
    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11190-4 PMID: 7479963
  15. Genetic control of chromosome length in yeast.
    Proc Natl Acad Sci U S A. 1985 Jan;82(2):506-10 PMID: 2982162
  16. Telomeres shorten during ageing of human fibroblasts.
    Nature. 1990 May 31;345(6274):458-60 PMID: 2342578
  17. Telomere reduction in human colorectal carcinoma and with ageing.
    Nature. 1990 Aug 30;346(6287):866-8 PMID: 2392154
  18. Hypervariable ultra-long telomeres in mice.
    Nature. 1990 Sep 27;347(6291):400-2 PMID: 2170845
  19. Telomeres: beginning to understand the end.
    Science. 1995 Dec 8;270(5242):1601-7 PMID: 7502069
  20. A human telomeric protein.
    Science. 1995 Dec 8;270(5242):1663-7 PMID: 7502076
  21. Human/mouse homology relationships.
    Genomics. 1996 May 1;33(3):337-51 PMID: 8660993
  22. Comparison of the human and mouse genes encoding the telomeric protein, TRF1: chromosomal localization, expression and conserved protein domains.
    Hum Mol Genet. 1997 Jan;6(1):69-76 PMID: 9002672
  23. A mammalian telomerase-associated protein.
    Science. 1997 Feb 14;275(5302):973-7 PMID: 9020079
  24. Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3 repeats.
    Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7423-8 PMID: 9207107
  25. Telomere length regulation during postnatal development and ageing in Mus spretus.
    Nucleic Acids Res. 1997 Aug 1;25(15):3051-8 PMID: 9224604
  26. Telomerase catalytic subunit homologs from fission yeast and human.
    Science. 1997 Aug 15;277(5328):955-9 PMID: 9252327
  27. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization.
    Cell. 1997 Aug 22;90(4):785-95 PMID: 9288757
  28. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2.
    Nat Genet. 1997 Oct;17(2):231-5 PMID: 9326950
  29. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA.
    Cell. 1997 Oct 3;91(1):25-34 PMID: 9335332
  30. Telomere lengthening and telomerase activation during human B cell differentiation.
    Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10827-32 PMID: 9380719
  31. Comparative gene mapping of the human and mouse TEP1 genes, which encode one protein component of telomerases.
    Genomics. 1997 Nov 15;46(1):46-50 PMID: 9403057
  32. Structure and function of telomeres.
    Nature. 1991 Apr 18;350(6319):569-73 PMID: 1708110
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1998-07-21
Pages
8648-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21130
Subset
IM
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