Biol Reprod
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

BOR - Papers in Press, published online ahead of print October 13, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.035030
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
72/2/487    most recent
biolreprod.104.035030v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gao, S.
Right arrow Articles by Latham, K. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gao, S.
Right arrow Articles by Latham, K. E.
Agricola
Right arrow Articles by Gao, S.
Right arrow Articles by Latham, K. E.
BIOLOGY OF REPRODUCTION 72, 487–491 (2005)
DOI: 10.1095/biolreprod.104.035030
© 2005 by the Society for the Study of Reproduction, Inc.

Recapitulation of the Ovum Mutant (Om) Phenotype and Loss of Om Locus Polarity in Cloned Mouse Embryos1

Shaorong Gao3, Guangming Wu3, Zhiming Han3, Elena de la Casa-Esperón3, Carmen Sapienza3,4, and Keith E. Latham2,3,5

The Fels Institute for Cancer Research and Molecular Biology,3 Department of Pathology,4 Department of Biochemistry,5 Temple University School of Medicine, Philadelphia, Pennsylvania 19140


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The ovum mutant (Om) locus in mice affects early interactions between sperm and egg that in turn affect viability of embryos beyond the morula stage. Crosses of DDK females to males of many other inbred strains are 95% lethal around the morula stage, whereas reciprocal crosses are fully viable. Available data indicate that the early lethality is the result of an interaction between a factor in the ooplasm and the paternal genome. In this study, we examined whether this lethal interaction would likewise occur in cloned embryos produced by somatic cell nuclear transfer. We find that the Om effect is recapitulated but that the parental origin effect at the Om locus is no longer evident in cloned embryos.

cloning, DDK syndrome, embryo, maternal effect, oocyte, somatic cell nuclear transfer


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The ovum mutant (Om) locus in mice affects early interactions between sperm and egg that in turn affect viability of embryos beyond the morula stage. Crosses of DDK-inbred-strain females to males of many other inbred strains (so-called alien strains [1]) are 95% lethal around the morula stage, whereas reciprocal crosses are fully viable [1–3] (Fig. 1). Ooplasm transfer, RNA microinjection, and pronuclear transfer studies all indicate that the early lethality is the result of an interaction between a factor in the ooplasm and the paternal genome [4–7]. The Om locus, residing on mouse chromosome 11 at position 48 cM [8– 10], encompasses a number of genes, at least one of which is believed to encode a maternally expressed ooplasmic factor and another believed to serve as the lethally interacting paternal gene, targeted by the ooplasmic factor [3, 8–10].



View larger version (17K):
[in this window]
[in a new window]
  		FIG. 1. Summary of interactions between DDK ooplasm and parental genomes documented in previous studies. Crossing DDK females to non-DDK males (alien) results in 95% lethality [1–3]. Crossing DDK females to DDK males results in normal viability. Introducing alien maternal or paternal pronuclei (PN) into DDK ooplasm results in lethality only with paternal pronuclei [5, 6]

Pronuclear transfer studies revealed that the interaction between the DDK ooplasm and a non-DDK pronucleus occurs with a paternal non-DDK pronucleus but not when maternal non-DDK pronuclei are introduced [5, 6] (Fig. 1). This observation indicates differential function of maternally and paternally derived non-DDK alleles in the genome of the early embryo, consistent with a role for genomic imprinting.

Somatic cell nuclear transfer (SCNT) methods employed for successful cloning [11, 12] require that the somatic cell nucleus be reprogrammed and then recapitulate early embryonic events leading to successful development of a new individual. The effect of the Om locus on development provides one informative means of evaluating whether early interactions between ooplasm and donor cell nucleus affecting early embryo viability are indeed recapitulated following SCNT. This means testing whether DDK-type ooplasm interacts with the lethally interacting locus present in a somatic cell nucleus in a manner similar to how it interacts with that locus obtained via a fertilizing sperm and whether the parental origin effect is still manifested within a somatic cell-derived genome. Additionally, SCNT provides a unique opportunity for examining the effects of the Om locus on development in the absence of a fertilizing sperm, making it possible to ascertain whether the Om locus effect is dependent on sperm chromatin, aspects of pronuclear formation, or sperm components introduced into the oocyte during fertilization. To meet these objectives, we performed SCNT using oocytes and cumulus cells from females homozygous for either DDK or non-DDK alleles at Om as well as cumulus cells from reciprocal F1 hybrids. We find that the early lethal effects of the Om locus are recapitulated in cloned embryos, but that the parental origin effect at this locus is not apparent in the context of SCNT.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Oocyte and Embryo Culture

Adult female mice were superovulated by sequential administration of 5 i.u. equine chorionic gonadotropin (eCG; Calbiochem, San Diego, CA) and human chorionic gonadotropin (hCG; Sigma-Aldrich, St. Louis, MO) 48 h apart. Oocytes and associated cumulus cells were obtained from (C57BL/6 x DBA/2)F1 females, denoted hereafter as (B6D2)F1 (Taconic, Germantown, NY). The (B6D2)F1 hybrids are homozygous for the non-DDK (alien) haplotype at Om, designated below as Oma/Oma. Other oocytes and cumulus cells were obtained from reciprocal crosses between C57BL/6J (The Jackson Laboratory, Bar Harbor, ME) and DDK/Pas individuals (breeding colony), denoted hereafter as Oma/Omk or Omk/Oma. Animals that were homozygous for the DDK haplotype over the entire Om region, but were otherwise of mixed DDK/Pas-C57BL/6 background, were initially generated from a cross between N2 animals (which are backcross offspring of (C57BL/6 x DDK)F1 and one of the inbred strain parents) and DDK/Pas [9, 10]. Siblings that were heterozygous for a recombinant chromosome 11 between markers D11Mit66 and D11Mit283 (the interval that includes Om [9, 10]—the recombinant chromosome 11 was designated 418E) were crossed to generate offspring homozygous for the 418E recombinant chromosome. Animals that are homozygous for this Omk-bearing recombinant chromosome 11 have been maintained by crossing the homozygous animals for more than 12 generations. The presence of the interstrain, polar-lethal Omk-associated phenotype has been confirmed by test crosses between 418E/418E females and DDK and C57BL/ 6 males (data not shown). Oocytes were cultured in CZB medium [13] supplemented with 5.5 mM glucose (CZB-G) [14]. Cloned constructs were cultured in minimal essential medium-{alpha} (MEM{alpha}) medium supplemented with 1 mM glutamine and 5 mg/ml BSA under an atmosphere of 5% CO2 and 21% O2 in nitrogen at 37°C in a humidified modular incubator (Billups-Rothenberg, Del March, CA). This culture system produces a high rate of preimplantation development (~60% blastocyst formation) and viable term development (2% of activated constructs) [15]. All studies adhered to procedures consistent with the National Research Council Guide for the Care and Use of Laboratory Animals.

Somatic Cell Nuclear Transfer and Oocyte Activation

Cloned embryos were produced as described [11] and later modified in our laboratory [12, 15] using cumulus cell donor nuclei of the genotypes indicated below. The use of dimethyl sulfoxide (DMSO) as a solvent for cytochalasin B (DMSO can affect cloned embryo development; [12]) was avoided by preparing a 1000x stock solution in ethanol. The concentration of polyvinylpyrolidone in the cell suspension medium was reduced to 3% to avoid toxic effects of higher concentrations. Embryos were injected in HEPES-buffered CZB-G, washed extensively, and then cultured in the media described above. Oocyte activation for parthenotes and clones was achieved by a 6-h incubation in calcium-free CZB-G supplemented with 10 mM SrCl2 and 5 µg/ml cytochalasin B [11]. The statistical significance of differences in development was evaluated using a Chi-squared test of independence to determine whether the proportion of embryos attaining blastocyst stage was affected by donor or recipient genotypes.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
DDK Syndrome in Cloned Constructs

Embryos from crosses of DDK females to non-DDK males exhibit arrested development between the morula and blastocyst stages [1, 3, 16], an effect that is mediated by an ooplasmic factor that interacts with a non-DDK paternal genome [4–7]. To determine whether the DDK ooplasm would likewise act on a non-DDK somatic cell-derived nucleus, we employed the SCNT method to transfer cumulus cell nuclei and then evaluate developmental potential of cloned constructs made with different combinations of donor and recipient genotypes. Preliminary studies revealed that the oocytes from females of the DDK/Pas inbred strain responded poorly (zero activated in two attempts) to the oocyte-activation method employed for cloning. Additionally, such oocytes were of limited availability. We therefore employed females of mixed DDK/Pas-C57BL/6 background (see Materials and Methods) that were homozygous for the DDK haplotype encompassing the entire Om region on chromosome 11 [10]. These females display the same DDK syndrome in crosses to non-DDK males as the DDK/ Pas inbred strain [10]. Unlike the parental DDK/Pas strain, however, the hybrid background allows these oocytes to be activated successfully using the standard SCNT activation protocol.

Among the four combinations of donor and recipient genotypes (A/A -> K/K, K/K -> K/K, K/K -> A/A, A/A -> A/A) that carried Omk alleles on both chromosomes or Oma alleles on both chromosomes all developed to the morula stage with good efficiency ([B6D2]F1 hybrids were used as the non-DDK nuclear donor and non-DDK ooplasm recipient, but both the C57BL/6 and DBA/2 Om alleles may be regarded as alien [1], CS unpublished]). Nuclei from Omk/ Omk cumulus cells produced slightly, but significantly, fewer morulae than nuclei from Oma/Oma cumulus cells, regardless of whether the recipient ooplasm was Omk/Omk or Oma/Oma (compare line 1, Table 1 with lines 2 and 4, Table 1). A much more pronounced effect of the donor nucleus genotype on blastocyst formation was observed, and this was dependent on oocyte strain of origin. Oocytes from (B6D2)F1 females (Oma/Oma) supported efficient development to blastocyst stage with either genotype of donor cell, although development was significantly reduced using Omk/Omk donor nuclei (lines 1 and 2, Table 1). In contrast, Omk/Omk oocytes supported efficient development to the blastocyst stage only when constructs were prepared with Omk/Omk cumulus cell nuclei (compare lines 4 and 5, Table 1). Blastocyst formation did not differ significantly between Omk/Omk or Oma/Oma oocytes receiving Omk/Omk nuclei (lines 2 and 4, Table 1). Conversely, blastocyst formation was severely inhibited in constructs prepared with Omk/ Omk oocytes and Oma/Oma cumulus cell nuclei (line 5, Table 1). In fact, the rate of conversion from morula to blastocyst was more than three times greater when Omk/Omk oocytes received Omk/Omk nuclei as compared with Oma/ Oma nuclei (lines 4 and 5, Table 1). This effect on the rate of conversion of morulae to blastocysts is in line with two earlier studies, in which micromanipulated zygotes displayed an approximately twofold effect on the rate of morula to blastocyst transition [5, 6]. Thus, the developmental arrest observed when non-DDK sperm fertilize Omk/Omk oocytes was recapitulated in constructs prepared with non-DDK somatic cell nuclei.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Interactions between donor cell nucleus genotype and ooplasm genotype.*

Lack of Imprinting Effect on DDK Syndrome in Clones

Although a non-DDK paternal pronucleus elicits the DDK syndrome in DDK oocytes, a non-DDK maternal pronucleus does not, as has been demonstrated in two separate studies employing different nuclear transfer strategies [5, 7]. To ascertain whether this parental origin effect persists in cloned constructs made with adult somatic cell nuclei, we produced clones by SCNT using cumulus cell nuclei from reciprocal F1 hybrid females (lines 6 and 7, Table 1). If the parental origin effect reflects imprinting at the Om locus and the imprinting persists in cumulus cells, nuclei from Oma/Omk females should support efficient blastocyst formation, while nuclei from Omk/Oma females (the rare survivors of matings between Omk/Omk females and Oma/ Oma males) should support greatly reduced development to blastocyst stage. This prediction was not fulfilled (Table 1 and Fig. 2). Embryos prepared with Omk/Omk recipients and either Oma/Omk or Omk/Oma donor nuclei developed to the blastocyst stage at a significantly lower rate than observed for those made with Omk/Omk donor cell nuclei (P < 0.001) and were not significantly differently from constructs prepared with Oma/Oma donor cell nuclei (P > 0.05). This relationship also applied when comparing the number of blastocysts obtained relative to those embryos attaining the morula stage. Donor nuclei from Oma/Omk cumulus cells transferred to Oma/Oma oocytes supported efficient blastocyst formation, indicating that the inability of reciprocal F1 nuclei to support development in Omk/Omk oocytes reflects a specific effect of the ooplasm. Thus, the effects of the somatic cell genome on cloning outcome are independent of parental origin of the alien allele at Om.



View larger version (113K):
[in this window]
[in a new window]
  		FIG. 2. Morphology of clone constructs after 4 (left column) and 5 (right column) days of culture. A and B) Morula and blastocysts stage clones prepared with A/K nuclei transplanted to K/K oocytes. C and D) Morula- and blastocysts-stage clones prepared with K/A nuclei transferred to K/K oocytes. E and F) Morula and blastocysts stage clones prepared with K/K nuclei transplanted to K/K oocytes. G and H) Morula- and blastocysts-stage clones prepared with A/A nuclei transplanted to A/A oocytes. The zona-enclosed embryos are approximately 90 µm in diameter. Photos were selected to illustrate the morphology and quality of surviving morulae and blastocysts and are not intended to reflect quantitative differences in developmental rates


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Early development in mammalian embryos is supported entirely by ooplasmic factors before embryonic genome transcription commences, and genetic variation in oocyte composition can have profound effects on early development [15, 17–24]. The polar-lethal ovum mutant (Om) phenotype is one of the most well-documented instances of such an effect and involves the interaction between the DDK ooplasm and the alien paternal genome. The data presented here indicate that this interaction is recapitulated in cloned embryos, with Omk/Omk ooplasm responding to non-DDK genomes in somatic cell nuclei just as it would to non-DDK genomes in paternal pronuclei. Other studies have revealed early effects of oocyte donor strain specifically on cloned embryos, including effects on culture medium preference, the incidence of two-cell stage arrest, and the rate of blastocyst formation [15]. Because cloning by SCNT involves the removal of the oocyte genome, these studies demonstrate unambiguously the effects of the ooplasm, independent of the oocyte genome, on nuclear function in early embryos. These observations also demonstrate the importance of accounting for such effects in the design of cloning approaches, with respect to selection of donor and recipient genotypes.

The recapitulation of the Om effect on somatic cell genomes indicates that a lethal interaction between the DDK ooplasmic factor and alien alleles at the Om locus occurs much as it does in DDK oocytes fertilized by an alien sperm genome. The molecular basis for this lethal interaction is unknown. Conceivably, a DDK ooplasmic factor may induce the expression of a gene that promotes lethality from the alien sperm genome, whereas this would not occur with a DDK sperm genome. Alternatively, the DDK ooplasm may suppress expression of an essential gene from the alien sperm genome but not from the DDK sperm genome. Whatever alien gene(s) is (are) normally affected by the DDK ooplasm appear to be affected similarly in the transplanted somatic cell genome. Thus, this component of the abnormal embryonic gene expression program induced in crosses between DDK females and alien males is reproduced in clones.

Pronuclear transfer studies have also revealed that the lethally interacting alien gene affected by the ooplasmic Omk factor must be inherited paternally because non-DDK maternal pronuclei failed to elicit the lethal effect [5, 6]. We can envision four mechanisms that could account for this result: 1) physical association of an alien sperm-derived factor with the paternal pronucleus; 2) differential timing or extent of transcriptional activation of maternal and paternal pronuclei [25–28]; 3) differential imprinting of the lethally interacting gene during gametogenesis such that only paternal alleles respond to the ooplasmic Omk factor; or 4) differential epigenetic modification of the two parental genomes after fertilization [20, 23, 28], involving either differential permeability of the pronuclear membranes or differential accessibility of chromatin to ooplasmic factors. We observe that Oma alleles in transplanted cumulus cell nuclei elicit the same Omk ooplasm-induced lethal effect, at the same developmental stage, as do Oma-containing paternal pronuclei (Table 1). This result excludes the first two of the above four mechanisms, as the lethal effect does not require either sperm-derived components or any unique aspect of pronuclear structure. Because the Om effect could be observed in cloned embryos, regardless of the parental origin of the Oma allele, some form of differential epigenetic modification is likely involved in the lethal interaction in fertilized embryos. This could involve either differential imprinting during gametogenesis or differential modification of maternal and paternal genomes after fertilization. If differential imprinting during gametogenesis is involved, then whatever imprint is responsible for the effect is either lost during development of the cumulus cells or is erased following nuclear transfer. If differential epigenetic modification of the two parental genomes after fertilization is involved, then whatever factors are responsible for the difference in the ability of maternal and paternal pronuclei to support this modification may be unique to pronuclear or preimplantation-stage genomes. Such postfertilization effects could follow from underlying differential modifications in the gamete genomes or could reflect differences in pronuclear envelopes or maternal and paternal chromatin that confers differential access of the Om ooplasmic factor to the target gene within the two pronuclei.

There is ample precedent in the literature for stage-specific or tissue-specific imprinting, as revealed by patterns of monoallelic and biallelic imprinted gene transcription [18, 19]. There is likewise ample precedent in the literature for disruptions in imprinting and in DNA methyltransferase expression in cloned embryos [29, 30]. In addition, there are many differences between maternal and paternal genomes at the pronuclear stage that might render them differentially sensitive to modification by factors present in the ooplasm [25–28]. Resolution of which of these mechanisms applies to the lethal effect in fertilized, as well as cloned, embryos awaits the identification and characterization of the gene(s) responsible.

Finally, we note that loss of the parental origin effect of the alien gene in cloned embryos argues for a mechanism in which the DDK ooplasm may elicit the expression of a lethality-inducing gene from the alien genome. The alternative mechanism, involving Omk ooplasm-induced suppression of a gene required for survival, would not be expected to affect the DDK allele of the responsive gene, thus making this mechanism unlikely. The ability of our data to distinguish between these possibilities provides a good illustration of the utility of SCNT methods to address fundamental questions related to molecular mechanisms controlling early development.


   ACKNOWLEDGMENTS
 
We are grateful to Fernando Pardo-Manuel de Villena for derivation and characterization of the 418E mice (see Materials and Methods) that are homozygous for the Omk haplotype on chromosome 11. We also thank Dr. Sue Varmuza for comments on the manuscript.


   FOOTNOTES
 
1 Supported in part by grants from the National Institute of Child Health and Human Development (NIH/NICHD) (HD 38381 to K.E.L. and HD34508 to C.S.) and the National Institute of General Medical Sciences (GM62537 to C.S.). Back

2 Correspondence: Keith E. Latham, 3307 North Broad St., Philadelphia, PA 19140. FAX: 215 707 1454; klatham{at}temple.edu Back

Received: 6 August 2004.

First decision: 30 August 2004.

Accepted: 21 September 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Wakasugi N. Studies on fertility of DDK mice: reciprocal crosses between DDK and C57BL/6J strains and experimental transplantation of the ovary. J Reprod Fertil 1973 33:283-291
  2. Wakasugi N, Tomita T, Kondo K. Differences of fertility in reciprocal crosses between inbred strains of mice. DDK, KK and NC. J Reprod Fertil 1967 13:41-50
  3. Wakasugi N. A genetically determined incompatibility system between spermatozoa and eggs leading to embryonic death in mice. J Reprod Fertil 1974 41:85-96
  4. Mann JR. DDK egg-foreign sperm incompatibility in mice is not between the pronuclei. J Reprod Fertil 1986 76:779-781
  5. Renard JP, Babinet C. Identification of a paternal developmental effect on the cytoplasm of one-cell-stage mouse embryos. Proc Natl Acad Sci U S A 1986 83:6883-6886[Abstract/Free Full Text]
  6. Babinet C, Richoux V, Guenet JL, Renard JP. The DDK inbred strain as a model for the study of interactions between parental genomes and egg cytoplasm in mouse preimplantation development. Development 1990 (suppl) 81-87
  7. Renard JP, Baldacci P, Richoux-Duranthon V, Pournin S, Babinet C. A maternal factor affecting mouse blastocyst formation. Development 1994 120:797-802[Abstract]
  8. Pardo-Manuel de Villena F, de la Casa-Esperon E, Verner A, Morgan K, Sapienza C. The maternal DDK syndrome phenotype is determined by modifier genes that are not linked to Om. Mamm Genome 1999 10:492-497[CrossRef][Medline]
  9. Pardo-Manuel de Villena F, Naumova AK, Verner AE, Jin WH, Sapienza C. Confirmation of maternal transmission ratio distortion at Om and direct evidence that the maternal and paternal "DDK syndrome" genes are linked. Mamm Genome 1997 8:642-646[CrossRef][Medline]
  10. Pardo-Manuel de Villena F, de La Casa-Esperon E, Williams JW, Malette JM, Rosa M, Sapienza C. Heritability of the maternal meiotic drive system linked to Om and high-resolution mapping of the Responder locus in mouse. Genetics 2000 155:283-289[Abstract/Free Full Text]
  11. Wakayama T, Perry ACF, Zuccotti M, Johnson KR, Yanagimachi R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 1998 394:369-374[CrossRef][Medline]
  12. Chung YG, Mann MR, Bartolomei MS, Latham KE. Nuclear-cytoplasmic ‘Tug-of-War’ during cloning: effects of somatic cell nuclei on culture medium preferences in the preimplantation cloned mouse embryo. Biol Reprod 2002 66:1178-1184[Abstract/Free Full Text]
  13. Chatot CL, Ziomek CA, Bavister BD, Lewis JL, Torres I. An improved culture medium supports development of random-bred one-cell mouse embryos in vitro. J Reprod Fertil 1989 86:679-688
  14. Kuretake S, Kimura Y, Hoshi K, Yanagimachi R. Fertilization of mouse oocytes injected with isolated sperm heads. Biol Reprod 1996 5:789-795
  15. Gao S, Czirr E, Chung YG, Han Z, Latham KE. Genetic variation in oocyte phenotype revealed through parthenogenesis and cloning: correlation with differences in pronuclear epigenetic modification. Biol Reprod 2004 70:1162-1170[Abstract/Free Full Text]
  16. Wakasugi N, Morita M. Studies on the development of F1 embryos from inter-strain cross involving DDK mice. J Embryol Exp Morphol 1977 38:211-216[Medline]
  17. Surani MA, Kothary R, Allen ND, Singh PB, Fundele R, Ferguson-Smith AC, Barton SC. Genome imprinting and development in the mouse. Development 1990 (suppl) 89-98
  18. Latham KE. Stage-specific and cell type-specific aspects of genomic imprinting effects in mammals. Differentiation 1995 59:269-282[Medline]
  19. Latham KE. Epigenetic modification and imprinting of the mammalian genome during development. Curr Top Dev Biol 1998 43:1-49
  20. Latham KE, Solter D. Effect of egg composition on the developmental capacity of androgenetic mouse embryos. Development 1991 113:561-568[Abstract]
  21. Reik W, Römer I, Barton SC, Surani MA, Howlett SK, Klose J. Adult phenotype in the mouse can be affected by epigenetic events in the early embryo. Development 1993 119:933-942[Abstract]
  22. Roemer I, Reik W, Dean W, Klose J. Epigenetic inheritance in the mouse. Curr Biol 1997 7:277-280[CrossRef][Medline]
  23. Howell CY, Steptoe AL, Miller MW, Chaillet JR. Cis-acting signal for inheritance of imprinted DNA methylation patterns in the preimplantation mouse embryo. Mol Cell Biol 1998 18:4149-4156[Abstract/Free Full Text]
  24. Howell CY, Bestor TH, Latham KE, Mertineit C, Trasler JM, Chaillet JR. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 2000 104:829-838
  25. Wiekowski M, Miranda M, DePamphilis ML. Requirements for promoter activity in mouse oocytes and embryos distinguish paternal pronuclei from maternal and zygotic nuclei. Dev Biol 1993 159:366-378[CrossRef][Medline]
  26. Aoki F, Worrad DM, Schultz RM. Regulation of transcriptional activity during the first and second cell cycles in the preimplantation mouse embryo. Dev Biol 1997 181:296-307[CrossRef][Medline]
  27. Adenot PG, Mercier YY, Renard JP, Thompson EM. Differential H4 acetylation of paternal and maternal chromatin precedes DNA replication and differential transcriptional activity in pronuclei of 1-cell mouse embryos. Development 1997 124:4615-4625[Abstract]
  28. Santos F, Hendrich B, Reik W, Dean W. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol 2002 241:172-182[CrossRef][Medline]
  29. Chung YG, Ratnam S, Chaillet JR, Latham KE. Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos. Biol Reprod 2003 69:146-153[Abstract/Free Full Text]
  30. Latham KE. Cloning: questions answered and unsolved. Differentiation 2004 72:11-22[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Biol. Reprod.Home page
F. Y. Ideraabdullah, K. Kim, D. Pomp, J. L. Moran, D. Beier, and F. P.-M. d. Villena
Rescue of the Mouse DDK Syndrome by Parent-of-Origin-Dependent Modifiers
Biol Reprod, February 1, 2007; 76(2): 286 - 293.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
T. A. Bell, E. de la Casa-Esperon, H. E. Doherty, F. Ideraabdullah, K. Kim, Y. Wang, L. A. Lange, K. Wilhemsen, E. M. Lange, C. Sapienza, et al.
The Paternal Gene of the DDK Syndrome Maps to the Schlafen Gene Cluster on Mouse Chromosome 11
Genetics, January 1, 2006; 172(1): 411 - 423.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
72/2/487    most recent
biolreprod.104.035030v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gao, S.
Right arrow Articles by Latham, K. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gao, S.
Right arrow Articles by Latham, K. E.
Agricola
Right arrow Articles by Gao, S.
Right arrow Articles by Latham, K. E.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS