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First published online January 25, 2006
doi: 10.1242/10.1242/dev.02221
Correspondence |
The Jackson Laboratory, Bar Harbor, MN 04609, USA
* Author for correspondence (e-mail: gridley{at}jax.org)
A recent paper in Development by Hahn and colleagues reports that
female mice homozygous for a targeted null mutation of the lunatic fringe
(Lfng) gene are infertile (Hahn et
al., 2005
). In 1998, our laboratory and Randy Johnson's laboratory
published independent papers on the construction and analysis of Lfng
knockout mice (Evrard et al.,
1998; Zhang and Gridley,
1998). The construct design of the targeted mutant alleles was
very similar. In both alleles, the first coding exon of the Lfng gene
was deleted, and embryos homozygous for either Lfng mutant allele
exhibited severe defects in somite formation. Hahn and colleagues obtained
Lfng mice from the Johnson laboratory for studies on oocyte
development and fertility. They reported that Lfng-/-
female mice did not mate, exhibited disorganized ovarian morphology and were
all infertile.
In their paper, Hahn et al. state that we reported previously that the
targeted Lfng mutation our group constructed `results in complete
embryonic lethality of Lfng-/- offspring'. Indeed, they
give that as the reason they obtained the Johnson Lfng mice for their
studies on folliculogenesis. However, we stated quite clearly, both in the
initial and in subsequent publications on these mice, that a large number of
our Lfng-/- null homozygotes are viable into adulthood
(Zhang and Gridley, 1998;
Zhang et al., 2000;
Zhang et al., 2002).
In addition, contrary to the findings of Hahn et al., at least some of our female Lfng-/- null homozygotes are fertile. Although we generally maintain our Lfng line by backcrossing or intercrossing Lfng+/- heterozygous mice, in a number of instances in the past 5 years we have mated Lfng-/- female homozygotes. While not every breeding pair set up becomes productive, many of these matings have proven to be fertile. We have frequently used matings to Lfng-/- females to generate mice for double-mutant studies. For example, we have mated Lfng-/- females to male mice containing mutations in the Notch1, Jag1, Dll3 and Rfng genes. In all of these cases, we had instances of productive matings in which Lfng-/- female homozygotes had multiple litters. Although we do not dispute that there is probably a role for Notch signaling in general, and the Lfng gene in particular, during ovarian follicle development in mice, the paper by Hahn et al. states that Lfng-/- female homozygotes are all infertile. Our results unequivocally demonstrate that, at least with respect to our Lfng mutant allele, this assertion is not true.
What then are the possible reasons for the discrepancy between the
fertility of Lfng-/- female mice of the two groups? One
possibility is that the two Lfng targeted alleles are functionally
different. This is possible, but seems quite unlikely given the similar
designs of the two Lfng alleles and the essentially identical somite
defects exhibited by the null homozygotes
(Evrard et al., 1998;
Zhang and Gridley, 1998). We
suggest that more likely possibilities include differences in genetic
background, and/or differences in mouse husbandry and colony conditions.
However, the assertions of Hahn et al. that mice homozygous for our
Lfng targeted mutation cannot survive postnatally and that
Lfng-/- female mice are obligatorily infertile are
incorrect.
REFERENCES
Evrard, Y. A., Lun, Y., Aulehla, A., Gan, L. and Johnson, R.
L. (1998). Lunatic fringe is an essential mediator of somite
segmentation and patterning. Nature
394,377
-381.[CrossRef][Medline]
Hahn, K. L., Johnson, J., Beres, B. J., Howard, S. and
Wilson-Rawls, J. (2005). Lunatic fringe null female mice are
infertile due to defects in meiotic maturation.
Development 132,817
-828.
Zhang, N. and Gridley, T. (1998). Defects in
somite formation in Lunatic fringe deficient mice.
Nature 394,374
-377.[CrossRef][Medline]
Zhang, N., Martin, G. V., Kelley, M. W. and Gridley, T.
(2000). A mutation in the Lunatic fringe gene suppresses the
effects of a Jagged2 mutation on inner hair cell development in the cochlea.
Curr. Biol. 10,659
-662.[CrossRef][Medline]
Zhang, N., Norton, C. R. and Gridley, T.
(2002). Segmentation defects of Notch pathway mutants and absence
of a synergistic phenotype in Lunatic fringe/Radical fringe double mutant
mice. Genesis 33,21
-28.[CrossRef][Medline]
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