Transgenic
λ Medaka as
a New Model for Germ Cell Mutagenesis
Richard
N.Winn1, Audrey J. Majeske2,3, Charles H. Jagoe2,
Travis C. Glenn2, Michael H. Smith2, and Michelle
B. Norris1
1Aquatic
Biotechnology and Environmental Laboratory, Warnell School of Forestry
and Natural Resources, University of Georgia, Athens, Georgia
2Environmental Health Sciences, Savannah River Ecology Laboratory,
University of Georgia, Aiken, South Carolina
3Biological Sciences, George Washington University, Washington
D.C.
Abstract:
To address the need for improved approaches to study mutations transmitted
to progeny from mutagen-exposed parents, we evaluated λ
transgenic medaka, a small fish that carries the cII mutation target
gene, as a new model for germ cell mutagenesis. Mutations in the cII
gene in progeny derived from ethyl-nitrosourea (ENU)-exposed males were
readily detected. Frequencies of mutant offspring, proportions of mosaic
or whole body mutant offspring, and mutational spectra differed according
to germ cell stage exposed to ENU. Postmeiotic germ cells (spermatozoa/late
spermatids) generated a higher frequency of mutant offspring (11%) compared
to premeiotic germ cells (3.5%). Individuals with cII mutant frequencies
(MF) elevated more than threefold above the spontaneous MF (3 x
10-5) in the range of 10-4 to 10-3 were
mosaic mutant offspring, whereas those with MFs approaching 1 x
10-2 were whole body mutant offspring. Mosaic mutant offspring
comprised the majority of mutant offspring derived from postmeiotic germ
cells, and unexpectedly, from spermatogonial stem cells. Mutational spectra
comprised of two different mutations, but at identical sites were unusual
and characteristic of delayed mutations, in which fixation of a second
mutation was delayed following fertilization. Delayed mutations and prevalence
of mosaic mutant offspring add to growing evidence that implicates germ
cells in mediating processes postfertilization that contribute to genomic
instability in progeny. This model provides an efficient and sensitive
approach to assess germ cell mutations, expands opportunities to increase
understanding of fundamental mechanisms of mutagenesis, and provides a
means for improved assessment of potential genetic health risks.
Keywords:
germline; genomic instability; mutations; cII gene
SREL Reprint #3086
Winn, R.
N., A. J. Majeske, C. H. Jagoe, T. C. Glenn, M. H. Smith and M. B. Norris.
2008. Transgenic λ
Medaka as
a New Model for Germ Cell Mutagenesis. Environmental and Molecular Mutagenesis
2008(49): 173-184.
