Departmet of Energy Oak Ridge National Laboratory Office of Science
systems genetics research facility
 
Dr. Liane B. Russell

Liane B. Russell
Keywords
Mouse genetics; germline mutagenesis; Heritable Mutations; Chromosome Aberrations

Education
A.B.: Hunter College
Ph.D.: University of Chicago

Research Area:

Basic mammalian genetics, mouse mutagenesis (radiations, chemicals), teratogenesis.

Description of Research:

Liane B. (Lee) Russell joined the Oak Ridge National Laboratory in 1947 and retired in 2002, continuing, however, on a guest assignment. Between 1975 and 1995 she served as head of the Mammalian Genetics & Development Section.

Dr. Russell's scientific contributions have been chiefly in the areas of basic mammalian genetics, mammalian mutagenesis, and teratogenesis. Early in her career, she carried out a systematic study of the effects of radiation on mouse embryos and fetuses which led to the definition of demarcated critical periods during prenatal development. Applying the findings of this classical teratogenetic study to human health, she suggested that elective radiation of women of childbearing age be restricted to the first two weeks of a menstrual cycle to avoid unsuspected pregnancies, a recommendation that has been accepted worldwide. She also developed the homeotic-shift method, a highly sensitive and quantitative prescreen for agents capable of causing developmental damage.

In the late 1950s, she and her co-workers established that the mammalian Y chromosome was male-determining and that XO, as well as XX, was female. Her subsequent discovery and analysis of variegated phenotypes produced by autosomal genes located in X-autosome translocations, led her to propose the single-active-X-chromosome hypothesis, published in 1961, simultaneously with (and differing slightly from) Lyon's inactive-X hypothesis. Russell's interest in mosaicism subsequently extended to mutations occurring during development, unstable genes, and abnormal segregation-fertilization events. Russell has also investigated the sterility of X-autosome-translocation males.

Making use of the large numbers of mutations generated over decades in the Oak Ridge mouse mutagenesis experiments, Russell carried out intensive complementation and other genetic analyses of chromosomal regions encompassing several specific loci. This work characterized large, well-populated deletion complexes, uncovered and localized numerous new functional units and genes within them, and provided the genetic tools for studying the effects of totally ablating defined chromosomal segments. It thereby provided the genetic skeletons on which subsequent molecular studies have built detailed functional/physical maps.

Reciprocally, the genetic analyses provided information about mutagenesis, specifically by demonstrating that the nature of induced mutations is related to the germ-cell type that was mutagenized, and to the type of mutagenic treatment administered. Russell also developed various assay systems for mammalian mutagenesis. One of these, the "mouse spot test" (an in vivo somatic-mutation method) has received use worldwide as a prescreen for heritable mutations.  Another, the numerical sex-chromosome anomaly method used genetic markers to test for the induction of non disjunction or chromosome loss. Among Russell's several other contributions to mutagenesis were: the chromosomal characterization of F1 male sterility, the identification of stages of high vulnerability (e.g., early pronuclear period), and the discovery of radiation-induced superovulation.


Recent Publications:
  • Russell, L.B. The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009.  Mutation Research-Reviews in Mutation Research, in press, 2013.
  • Russell, L.B., and P. R. Hunsicker.  The effect of dose rate on the frequency of specific-locus mutations induced in mouse spermatogonia is restricted to larger lesions; a retrospective analysis of historical data.  Radiation Research, 177:555-564, 2012.
  • Russell, L. B., P. R. Hunsicker, and W. L Russell. Comparison of the genetic effects of equimolar doses of ENU and MNU: while the chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia, both elicit very high mutation rates in differentiating spermatogonia. Mutation Research, 616:181-195, 2007.
  • Russell, L. B. Effects of male germ-cell stage on the frequency, nature, and spectrum of induced specific-locus mutations in the mouse. Genetica 122(1):25-36, 2004.
  • Russell, L. B., P. R. Hunsicker, M. K. Kerley, A.Pyle, and A.M. Sexton. Etoposide exposure during male mouse pachytene has complex effects on crossing-over and causes nondisjunction. Mutation Research, 565:61-77, 2004.
  • Rajaraman, S, L.K. Wood, D.K. Willhite, L. B. Russell, and M. A. Bedell. Effects of spontaneous KitlSteel mutations on survival and anemia of mice. Mammalian Genome, 3:168-74, 2003.
  • Rajaraman, S, W. S. Davis, A. Mahakali-Zama, H. K. Evans, L. B. Russell, and M. A. Bedell. An allelic series of mutations in the Kit ligand (Kitl) gene of mice. I. Identification of point mutations in seven ENU-induced KitlSteel alleles. Genetics, 162:331-340, 2002.
  • Rajaraman, S, W. S. Davis, A. Mahakali-Zama, H. K. Evans, L. B. Russell, and M. A. Bedell. An allelic series of mutations in the Kit ligand (Kitl) gene of mice. II. Effects of point mutations on survival and peripheral blood cells of KitlSteel mice. Genetics, 162:341-353, 2002.
  • Miltenberger, R.J., K. Wakamatsu, S. Ito, R.P. Woychik, L.B. Russell, and E.J. Michaud. Molecular and phenotypic analysis of 25 recessive, homozygous-viable alleles at the mouse agouti locus. Genetics 160: 659-674 (February 2002).
  • Nadeau, J.H. et al. (39 names). Functional annotation of mouse genome sequences. Science 291:1251-1255, 16 Feb. 2001.
  • Johnson, D. K., Carpenter, D.A., Culiat, C.T., Goss, K.A., Klebig, M.L., Michaud, E.J., Miller, D.R., Russell, L.B., You, Y., and Rinchik, E.M. A phenotype-driven approach to the molecular and functional analysis of the mouse genome. In, Microbial Status and Genetic Evaluation of Mice and Rats, Proceedings of the 1999 US/Japan meeting, National Research Council, Washington DC, pp. 105-115, 2000.
  • Russell, L. B., and W. L. Russell.  Spontaneous mutations recovered as mosaics in the mouse specific-locus test.  Proc. Natl. Acad. Sci. USA. 93:13072-13077, Nov. 1996. Brief correction added in Proc. Natl. Acad. Sci. USA. 94:4233, 1997.
  • Marker, P. C., K. Seung, A. E. Bland, L. B. Russell, and D. M. Kingsley. Spectrum of Bmp5 mutations from germ-line mutagenesis experiments in mice. Genetics. 145:435-443, 1997.
  • DiLeone, R. J., L. B. Russell, and D. M. Kingsley. An extensive 3' regulatory region controls expression of Bmp5 in specific anatomical structures of the mouse embryo. Genetics, 148:401-408, January 1998.
  • Russell, L. B., P. R. Hunsicker, D. K. Johnson, and M. D. Shelby. Unlike other chemicals, etoposide (a topoisomerase-II inhibitor) produces peak mutagenicity in primary spermatocytes of the mouse. Mutation Research, 400:279-286, 1998.
  • Huang, J.-D., M. J. T. V. Cope, V. Mermall, M. C. Strobel, J. Kendrick-Jones, L. B. Russell, M. S. Mooseker, N. G. Copeland, amd N. A. Jenkins. Molecular genetic dissection of unconventional myosin-VA: Head region mutations. Genetics, 148:1951-1961, April 1998.
  • Huang, J.-D., V. Mermall, M. C. Strobel, L. B. Russell, M. S. Mooseker, N. G. Copeland, and N. A. Jenkins. Molecular genetic dissection of unconventional myosin-VA: Tail region mutations. Genetics, 148:1963-1972, April 1998.
  • Russell, W. L., J. W. Bangham, and L. B. Russell.  Differential response of mouse male germ-cell stages to radiation-induced specific-locus and dominant mutations.  Genetics, 148:1567-1578, April 1998.
  • Shin. M., Russell, L.B. and Tilghman, S.M. Molecular characterization of four induced alleles at the Ednrb locus. Proc. Nat. Acad. Sci. USA, 94:13105-13110, 1997.
  • Russell, L. B.  Significance of the perigametic interval as a major source of spontaneous mutations that result in mosaics. Enviromental and Molec. Mutagenesis, 34:16-23, 1999.
  • Russell, L. B., P. R. Hunsicker, A. M.  Hack, and T. Ashley.  Effect of the topoisomerase-II inhibitor etoposide on meiotic recombination in male mice.  Mutation Research, in press, 1999.
  • Russell, L. B., P. R. Hunsicker, M. K. Kerley, D. K. Johnson, and M. D. Shelby. Bleomycin, unlike other male-mouse mutagens, is most effective in spermatogonia, inducing primarily deletions. Mutation Research, 469(1):95-105, 2000.
  • Colella, T. A., T. N. J. Bullock, L. B. Russell, D. W. Mullins, W. W. Overwijk, C. J. Luckey, R. A. Pierce, N. P. Restifo, and V. H. Engelhard. Self-tolerance to the murine homologue of a tyrosinase-derived melanoma antigen: Implications for tumor immunotherapy. J. Exptl. Medicine, 191(7):1221-1231, 2000.
  • Walkowicz, M., Y. Ji, X. Ren, B. Horsthemke, L. B. Russell, D. Johnson, E. M. Rinchik, R. D. Nicholls, L. Stubbs. Molecular characterization of radiation- and chemically-induced mutations associated with neuromuscular tremors, runting, juvenile lethality, and sperm defects in jdf2 mice.
  • Mammalian Genome 10:870-878, 1999.
  • Wilson, S.M., R. Yip, D. A Swing, T. N. O'Sullivan, T. Zhang, E. K. Novak, R. T. Swank, L. B. Russell, N. G. Copeland, and N. A. Jenkins. A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proc. Nat. Acad. Sci. USA, 97(14):7933-7938, 2000.
Selected Publications
  • Russell, L.B. The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009.  Mutation Research-Reviews in Mutation Research, in press, 2013.
  • Russell, L.B., and P. R. Hunsicker.  The effect of dose rate on the frequency of specific-locus mutations induced in mouse spermatogonia is restricted to larger lesions; a retrospective analysis of historical data.  Radiation Research, 177:555-564, 2012.
  • Russell, Liane Brauch. X-ray induced developmental abnormalities in the mouse and their use in the analysis of embryological patterns. I. External and gross visceral changes. J. Exptl. Zool. 114:545-602, 1950.
  • Russell, Liane Brauch and W. L. Russell. Radiation hazards to the embryo and fetus. Radiology 58:369-376, 1952.
  • Russell, Liane Brauch, and W. L. Russell. An analysis of the changing radiation response of the developing mouse embryo. J. Cellular Comp. Physiol. 43, Suppl. 1:103-149, 1954.
  • Russell, Liane Brauch and Mary H. Major. Radiation-induced presumed somatic mutations in the house mouse. Genetics 42:161-175, 1957.
  • Russell, W. L., Liane Brauch Russell and Josephine Gower. Exceptional inheritance of a sex-linked gene in the mouse explained on the basis that the X/0 sex-chromosome constitution is female. Proc. Nat. Sci. U.S. 45:554-560, 1959.
  • Welshons, W. J. and Liane Brauch. The Y-chromosome as the bearer of male-determining factors in the mouse. Proc. Nat. Acad. Sci. U.S. 45:560-566, 1959.
  • Russell, Liane Brauch and Jean W. Bangham. Variegated-type position effects in the mouse. Genetics 46:509-525, 1961.
  • Russell, Liane Brauch. Genetics of mammalian sex chromosomes. Science 133:1795-1803, 1961.
  • Russell, Liane Brauch. Chromosome Aberrations in Experimental Mammals. In, PROGRESS IN MEDICAL GENETICS, Vol. 2, eds. A. G. Steinberg and A. G. Bearn. Grune & Stratton, Inc., New York, pp. 230-294, 1962.
  • Russell, Liane Brauch. Mammalian X-chromosome action: inactivation limited in spread and in region of origin. Science 140:976-978, 1963.
  • Russell, Liane B. Genetic and functional mosaicism in the mouse. In, "The Role of Chromosomes in Development", ed. Michael Locke. Academic Press, Inc. (New York), pp. 153-181, 1964.
  • Russell, Liane Brauch and Florence N. Woodiel. A spontaneous mouse chimera formed from separate fertilization of two meiotic products of oogenesis. Cytogenetics 5:106-119, 1966.
  • Russell, Liane B. Definition of functional units in a small chromosomal segment of the mouse and its use in interpreting the nature of radiation-induced mutations. Mutation Res. 11:107-123, 1971.
  • Russell, Liane Brauch. Numerical sex-chromosome anomalies in mammals: their spontaneous occurrence and use in mutagenesis studies. In, "Chemical Mutagens - Principles and Methods for Their Detection," Vol.4, Ed. A. Hollaender, Plenum Press (New York), pp. 55-91, 1976.
  • Russell, Liane B. In vivo somatic mutation systems in the mouse. Genetics 92:s153-s163, 1979.
  • Russell, Liane B. Sensitivity patterns for the induction of homeotic shifts in a favorable strain of mice. Teratology 20:115-125, 1979.
  • Russell, Liane B. Meiotic nondisjunction in the mouse: methodology for genetic testing and comparison with other methods. Env. Health Persp. 31:113-128, 1979.
  • Russell, L. B., C. S. Montgomery, and G. D. Raymer. Analysis of the albino-locus region of the mouse: IV. Characterization of 34 deficiencies. Genetics 100:427-453, 1982.
  • Russell, L. B. and C. S. Montgomery. Supermutagenicity of ethylnitrosourea in the mouse spot test; comparisons with methylnitrosourea and ethylnitrosourethane. Mutation Research 92:193-204, 1982.
  • Russell, L. B., W. L. Russell, E. M. Rinchik and P. R. Hunsicker. Factors Affecting the Nature of Induced Mutations. In: Banbury Report 34: Biology of Mammalian Germ Cell Mutagenesis, Cold Spring Harbor Laboratory press, pp 271-289, 1990.
  • Russell, Liane B. X-autosome translocations in the mouse: their characterization and use as tools to investigate gene inactivation and gene action. In, "Cytogenetics of the Mammalian X Chromosome, Part A: Basic Mechanisms of X Chromosome Behavior," Ed. A. A. Sandberg, Progress and Topics in Cytogenetics, Vol. 3A, pp. 205-250, 1983.
  • Russell, Liane B. Experimental approaches for the detection of chromosomal malsegregation occurring in the germline of mammals. In, "Aneuploidy: Etiology and Mechanisms," Eds. Dellarco, et al., Plenum Press (New York), pp. 377-396, 1985.
  • Russell, L. B., J. W. Bangham, K. F. Stelzner, and P. R. Hunsicker. High frequency of mosaic mutants produced by N-ethyl-N-nitrosourea exposure of mouse zygotes. Proc. Natl. Acad. Sci., USA, 85: 9167-9170, 1988.
  • Russell, L. B., W. L. Russell, E. M. Rinchik and P. R. Hunsicker. Factors Affecting the Nature of Induced Mutations. In: Banbury Report 34: Biology of Mammalian Germ Cell Mutagenesis, Cold Spring Harbor Laboratory press, pp 271-289, 1990.
  • Rinchik, E. M. and L. B. Russell. 1990. Germ-Line Deletion Mutations in the Mouse: Tools for Intensive Functional and Physical Mapping of Regions for the Mammalian Genome. In: "Genome Analysis," Eds. K. Davies and S. Tilghman, Genetic and Physical Mapping, Vol. 1, Cold Spring Harbor Laboratory Press (New York), pp. 121-158, 1990.
  • Russell, L. B. and W. L. Russell. Frequency and nature of specific-locus mutations induced in female mice by radiations and chemicals: a review. Mutat. Res. 296:107-127, 1992.
  • Russell, L. B., C. S. Montgomery, N.L.A. Cacheiro, and D. K. Johnson. Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse. Genetics 141:1547-1562, Dec. 1995.
  • Russell, L. B., and W. L. Russell. Spontaneous mutations recovered as mosaics in the mouse specific-locus test. Proc. Natl. Acad. Sci. USA. 93:13072-13077, Nov. 1996. Brief correction added in Proc. Natl. Acad. Sci. USA. 94:4233, 1997.
  • Russell, W. L., J. W. Bangham, and L. B. Russell. Differential response of mouse male germ-cell stages to radiation-induced specific-locus and dominant mutations. Genetics, 148:1567-1578, April 1998.
  • Russell, L. B. Significance of the perigametic interval as a major source of spontaneous mutations that result in mosaics. Enviromental and Molec. Mutagenesis, 34:16-23, 1999.
  • Rusell, L. B. Effects of male germ-cell stage on the frequency, nature, and spectrum of induced specific-locus mutations in the mouse. Genetica, in press.
Honors and Awards
  • Scientific Advisor to U.S. Delegation at First Atoms for Peace Conference, Geneva, 1955.
  • MADEMOISELLE Merit Award for outstanding woman, 1955.
  • Nominated for Newcomb Cleveland Prize of AAAS, 1961.
  • Fellow, AAAS, 1963.
  • Roentgen Medal (International Award), 1973.
  • Hunter College (City University of New York) Hall of Fame, 1979.
  • Genetics Soc. of America, Presidential Nominee, 1979.
  • President, Environmental Mutagen Soc., 1984.
  • Union Carbide, Corporate Fellow, 1983.
  • National Academy of Sciences, Member, 1986.
  • U.S. Department of Energy, Distinguished Associate Award, 1987.
  • Sol Feinstone Environmental Achievement Award, State Univ. of New York, 1987.
  • Martin Marietta Energy Systems, Senior Corporate Fellow, 1988.
  • Martin Marietta Energy Systems, Technical Achievement Award, 1988.
  • Tennessee Environmental Council Lifetime Achievement Award, 1990.
  • Rotary Club Vocational Service Award, 1992.
  • Environmental Mutagen Society's EMS Award, 1993.
  • National Parks Conservation Association's Marjorie Stoneman Douglas Award, 1993.
  • Enrico Fermi Award, 1993 Award (presented 1/26/95).
  • Tennessee Environmental Honor Society, 1998
  • Honorary Doctor of Science, Hunter College, City University of New York, January 1999
  • Lifetime Environmental/Conservation Award, Tenn. Dept. of Environment & Conservation, 2000
  • Lifetime Conservation Award, Southern Appalachian Forest Coalition
  • Honorary Doctor of Humane Letters, Berea College, KY, December 2005
Contact Information for Dr. Liane B. Russell
Corporate Fellow, retired
Oak Ridge National Laboratory
System Genetics
Biosciences Division
Oak Ridge, TN 37831-6420

Telephone: (865) 574-0860
Fax: (865) 574-1283
E-mail: lianerussell@comcast.net
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