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First published online January 25, 2006
doi: 10.1242/10.1242/dev.02222
Response |
1 School of Life Sciences, Arizona State University, Tempe, AZ 85287-4501,
USA
2 Yale School of Medicine, Department of OB/GYN and Reproductive Sciences, 333
Cedar Street, New Haven, CT 06510, USA
* Author for correspondence (e-mail: nrawls{at}imap4.asu.edu)
The Wilson-Rawls laboratory was the first to describe the dynamic
expression pattern of genes of the Notch signaling pathway in mammalian
ovarian follicles (Johnson et al.,
2001
). In a recent report (Hahn
et al., 2005), we described a completely penetrant infertility
phenotype in female mice that are homozygous null for a lunatic fringe
(Lfng) mutant allele, previously described by Evrard et al.
(Evrard et al., 1998).
Furthermore, we characterized defects in follicle development and meiotic
maturation that correlate with a loss of expression of the Notch downstream
target effector genes in follicles (Hahn et
al., 2005). These data are consistent with our conclusion that
Lfng and the Notch signaling pathway have an important role to play in ovarian
folliculogenesis.
Xu and colleagues now report anecdotal evidence that some mice homozygous
for a Lfng mutant allele (LfnglacZ) generated in
their laboratory are fertile and were used occasionally in the generation of
more LfnglacZ/lacZ mutants, as well as for the generation
of compound mutations of Lfng and other genes in the Notch pathway
(Xu et al., 2006). We note that
this breeding strategy is not described in papers published by the Gridley
laboratory. In fact, where a breeding strategy was described, the authors have
bred LfnglacZ/+ animals to generate homozygous
LfnglacZ/lacZ mutants
(Zhang and Gridley, 1998;
Zhang et al., 2002). However,
Xu et al. concede that not all of the LfnglacZ/lacZ
matings are productive. In other words, consistent with our observations, a
lack of lunatic fringe is associated with infertility. These observations do
not dispute our central conclusion that Lfng is important in ovarian
folliculogenesis, but instead provide new information regarding the penetrance
of the infertility phenotype in the two mutant alleles of Lfng.
Genetic mutations in mice are powerful tools for examining the contribution
of specific genes to complex biological processes, such as folliculogenesis.
Interpreting specific gene mutations can be confounded by variations in the
penetrance of phenotypic defects in the same genetic background, as well as in
different genetic backgrounds (Beck et al.,
2000; Chia et al.,
2005). Furthermore, variations in the severity of the phenotype
can occur between mutant alleles generated in different laboratories. In the
case of Lfng, mice homozygous for either mutant allele experience
radical disruptions in the organization of the axial skeleton owing to a
failure of the proper segmentation of the somites
(Evrard et al., 1998;
Zhang and Gridley, 1998).
Despite similarities in their gross morphology, there was a greater loss of
somite epithelialization in the Lfng-/- embryos when
compared with the LfnglacZ/lacZ embryos
(Evrard et al., 1998;
Zhang and Gridley, 1998).
Perhaps it is not surprising that additional studies with these mice are
revealing additional differences. Indeed, a careful analysis of fertility and
fecundity rates in the LfnglacZ mice would offer an
excellent comparison and contrast to the strain of mice used in our studies.
None of this, however, refutes our conclusion that Lfng and, by extension,
Notch signaling are important regulators of folliculogenesis.
REFERENCES
Beck, J. A., Lloyd, S., Hafezparast, M., Lennon- Pierce, M., Eppig, J. T., Festing, M. F. W. and Fisher, E. M. C. (2000). Genealogies of mouse inbred strains. Nat. Genet. 24, 23-25.[CrossRef][Medline]
Chia, R., Achilli, F., Festing, M. F. W. and Fisher, E. M. C. (2005). The origins and uses of mouse outbred stocks. Nat. Genet. 37,1181 -1186.[CrossRef][Medline]
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.
Johnson, J., Espinoza, T., McGaughey, R. W., Rawls, A. and Wilson-Rawls, J. (2001). Notch pathway genes are expressed in mammalian ovarian follicles. Mech. Dev. 109,355 -361.[CrossRef][Medline]
Xu, J., Norton, C. R. and Gridley, T. (2006).
Not all lunatic fringe null mice are infertile.
Development 133,579
.
Zhang, N. and Gridley, T. (1998). Defects in somite formation in Lunatic fringe deficient mice. Nature 394,374 -377.[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]
This article has been cited by other articles:
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  K. L. Hahn, J. Johnson, B. J. Beres, and J. Wilson-Rawls A loss of lunatic fringe is associated with female infertility Development, February 15, 2006; 133(4): 579 - 580. [Full Text] [PDF]
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