Parthenogenetic embryos, which contained one genome from a neonate-derived non-growing oocyte and the other from a fully grown oocyte, developed to day 13.5 of gestation in mice, 3 days longer than previously recorded for parthenogenetic development. To investigate the hypothesis that disruption of primary imprinting during oocyte growth leads to the modified expression of imprinted genes and this parthenogenetic phenotype, we have examined Peg1/Mest, Igf2, Peg3, Snrpn, H19, Igf2r and excess p57KIP2. We show that paternally expressed genes, Peg1/Mest, Peg3 and Snrpn, are expressed in the parthenotes, presumably due to a lack of maternal epigenetic modifications during oocyte growth. In contrast, the expression of Igf2, which is repressed in a competitive manner by transcription of the H19 gene, was very low. Furthermore, we show that the maternally expressed Igf2r and p57KIP2 genes were repressed in the alleles of the non-growing oocyte indicating maternal modifications during oocyte growth are necessary for its expression. Thus, our results show that primary imprinting during oocyte growth exhibits a crucial effect on both the expression and repression of maternal alleles during embryogenesis.
REFERENCES
Baker
J.
, Liu
J. P.
, Robertson
E. J.
, Efstratiadis
A.
(1993
) Role of insulin-like growth factors in embryonic and placental growth.
Cell
75
, 73
–82
Barlow
D. P.
, Stöger
R.
, Herrmann
B. G.
, Saito
K.
, Schweifer
N.
(1991
) The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus.
Nature
349
, 84
–87
Barr
J. A.
, Jones
J.
, Glenister
P. H.
, Cattanach
B. M.
(1995
) Ubiquitous expression and imprinting of Snrpn in the mouse.
Mamm. Genome
6
, 405
–407
Bartolomei
M. S.
, Webber
A. L.
, Brunkow
M. E.
, Tilghman
S. M.
(1993
) Epigenetic mechanisms underlying the imprinting of the mouse H19 gene.
Genes Dev
7
, 1663
–1673
Bartolomei
M. S.
, Zemel
S.
, Tilghman
S. M.
(1991
) Parental imprinting of mouse H19 gene.
Nature
351
, 153
–155
Barton
S. C.
, Surani
M. A. H.
, Norris
M. L.
(1984
) Role of paternal and maternal genomes in mouse development.
Nature
311
, 374
–376
Brunkow
M. E.
, Tilghman
S. M.
(1991
) Ectopic expression of the H19 gene in mice causes prenatal lethality.
Genes Dev
5
, 1092
–1101
Cattanach
B. M.
, Beechey
C. V.
(1990
) Autosomal and X-chromosome imprinting.
Development
1990
, 63
–72
Cattanach
B. M.
, Barr
J. A.
, Evans
E. P.
, Burtenshaw
M.
, Beechey
C. V.
, Leff
S. E.
, Brannan
C. I.
, Copeland
N. G.
, Jenkins
N. A.
, Jones
J.
(1992
) A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression.
Nature Genet
2
, 270
–274
DeChiara
T. M.
, Robertson
E. J.
, Efstratiadis
A.
(1991
) Paternal imprinting of the mouse insulin-like growth factor II gene.
Cell
64
, 849
–959
Ferguson-Smith
A. S.
, Cattanach
B. M.
, Barton
S. C.
, Beechey
C. V.
, Surani
M. A.
(1991
) Embryological and molecular investigations of parental imprinting on mouse chromosome 7.
Nature
351
, 667
–670
Gardner
R. L.
, Barton
S. C.
, Surani
M. A. H.
(1990
) Use of triple tissue blastocyst reconstitution to study the development of diploid parthenogenetic primitive ectoderm in combination with fertilization-derived trophectoderm and primitive endoderm.
Genet Res
56
, 209
–222
Guillemot
F.
, Caspary
T.
, Tilghman
S. M.
, Copeland
N. G.
, Gilbert
D.J.
, Jenkins
N. A.
, Aderson
D.
, Joyner
A. L.
, Rossant
J.
, Nagy
A.
(1995
) Genomic imprinting of Mash2, a mouse gene required for trophoblast development.
Nature Genet
9
, 235
–242
Hatada
I.
, Mukai
T.
(1995
) Genomic imprinting of p57 KIP2, a cyclin-dependent kinase inhibitor, in mouse.
Nature Genet
11
, 204
–206
Kaneko-Ishino
T.
, Kuroiwa
Y.
, Miyoshi
N.
, Kohda
T.
, Suzuki
R.
, Yokoyama
M.
, Viville
S.
, Barton
S. C.
, Ishino
F.
, Surani
M. A.
(1995
) Peg1/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization.
Nature Genet
11
, 52
–59
Kono
T.
, Obata
Y.
, Yoshimizu
T.
, Nakahara
T.
, Carroll
J.
(1996
) Epigenetic modifications during oocyte growth correlates with extended parthenogenetic development in the mouse.
Nature Genet
13
, 91
–94
Kuroiwa
Y.
, Kaneko-Ishino
T.
, Kagitani
F.
, Kohda
T.
, Li
L. L.
, Tada
M.
, Suzuki
R.
, Yokoyama
M.
, Shiroishi
T.
, Wakana
S.
, Barton
S. C.
, Ishino
F.
, Surani
M. A.
(1996
) Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger.
Nature Genet
12
, 186
–190
Kwon
O. Y.
, Kono
T.
(1996
) Production of identical sextuplet mice by transferring metaphase nuclei from four-cell embryos.
Proc. Natl. Acad. Sci. USA
93
, 13010
–13013
Lau
M. M. H.
, Stewart
C. E. H.
, Liu
Z.
, Bhatt
H.
, Rotwein
P.
, Stewart
C. L.
(1994
) Loss of the imprinted IGF2/cation independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality.
Genes Dev
8
, 2953
–2963
Leighton
P. A.
, Saam
J. R.
, Ingram
R. S.
, Stewart
C. L.
, Tilghman
S. M.
(1995
) An enhancer deletion affects both H19 and Igf2 expression.
Genes Dev
9
, 2079
–2089
Lescisin
K. R.
, Varmuza
S.
, Rossant
J.
(1988
) Isolation and characterization of a novel trophoblast-specific cDNA in the mouse.
Genes Dev
2
, 1639
–1646
Li
E.
, Beard
C.
, Jaenisch
R.
(1993
) Role for DNA methylation in genomic imprinting.
Nature
366
, 362
–365
Marahrens
Y.
, Panning
B.
, Dausman
J.
, Strauss
W.
, Jaenisch
R.
(1997
) Xist -deficient mice are defective in dosage compensation but not spermatogenesis.
Genes Dev
11
, 156
–166
McLaughlin
K. J.
, Szabo
P.
, Haegel
H.
, Mann
J. R.
(1996
) Mouse embryos with paternal duplication of an imprinted chromosome 7 region die at midgestation and lack placental spongiotrophoblast.
Development
122
, 265
–270
Nakao
M.
, Sasaki
H.
(1996
) Genomic imprinting: Significance in development and diseases and the molecular mechanisms.
Nature
362
, 751
–755
O'Neill
G. T.
, Rolfe
L. R.
, Kaufman
M. H.
(1991
) Developmental potential and chromosome constitution of strontium-induced mouse parthenogenones.
Mol. Reprod. Dev
30
, 214
–219
Ohlsson
R.
, Holmgren
L.
, Glaser
A.
, Szpecht
A.
, Pfeifer-Ohlsson
S.
(1989
) Insulin-like growth factor 2 and short-range stimulatory loops in control of human placental growth.
EMBO J
8
, 1993
–1999
Sado
T.
, Nakajima
N.
, Tada
M.
, Takagi
N.
(1993
) A novel mesoderm-specific cDNA isolated from a mouse embryonal carcinoma cell line.
Dev. Growth Differ
35
, 551
–560
Sasaki
H.
, Ferguson-Smith
A. C.
, Shum
A. S. W.
, Barton
S. C.
, Surani
M. A.
(1995
) Temporal and spatial regulation of H19 imprinting in normal and uniparental mouse embryos.
Development
121
, 4195
–4202
Sasaki
H.
, Jones
P. A.
, Chaillet
J. R.
, Ferguson-Smith
A. C.
, Barton
S. C.
, Reik
W.
, Surani
M. A.
(1992
) Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene.
Genes Dev
6
, 1843
–1856
Stöger
R.
, Kubicka
P.
, Liu
C. G.
, Kafri
T.
, Razin
A.
, Cedar
H.
, Barlow
D. P.
(1993
) Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal.
Cell
73
, 61
–71
Surani
M. A. H.
, Barton
S. C.
, Norris
M. L.
(1984
) Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis.
Nature
308
, 548
–550
Sutcliffe
J. S.
, Nakao
M.
, Christina
S.
, Orstavik
K. H.
, Tommerup
N.
, Ledbetter
D. H.
, Beaudet
A. L.
(1994
) Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region.
Nature Genet
8
, 52
–58
Walsh
C.
, Glaser
A.
, Fundele
R.
, Ferguson-Smith
A.
, Barton
S.
, Surani
M. A.
, Ohlsson
R.
(1994
) The non-viability of uniparental mouse conceptuses correlates with the loss of the products of imprinted genes.
Mech. Dev
46
, 55
–62
Wutz
A.
, Smrzka
O. W.
, Schweifer
N.
, Schellander
K.
, Wagner
E. F.
, Barlow
D. P.
(1997
) Imprinted expression of the Igf2r gene depends on an intronic CpG island.
Nature
389
, 745
–749
Yan
Y.
, Frisen
J.
, Lee
M. H.
, Massague
J.
, Barbacid
M.
(1997
) Ablation of the CDK inhibitor p57 KIP2 results in increased apoptosis and delayed differentiation during mouse development.
Genes Dev
11
, 973
–983
Yoo-Warren
H.
, Pachnis
V.
, Ingram
R. S.
, Tilghman
S. M.
(1988
) Two regulatory domains flank the mouse H19 gene.
Mol. Cell. Biol
8
, 4707
–4715
Zechner
U.
, Reule
M.
, Orth
A.
, Bonhomme
F.
, Strack
B.
, Guenet
J. L.
, Hameister
H.
, Fundele
R.
(1996
) An X-chromosome linked locus contributes to abnormal placental development in mouse interspecific hybrids.
Nature Genet
12
, 398
–403
Zemel
S.
, Bartolomei
M. S.
, Tilghman
S. M.
(1992
) Physical linkage of two mammalian imprinted genes, H19 and insulin-like growth factor 2.
Nature Genet
2
, 61
–65
Zhang
P.
, Liegeois
N. J.
, Wong
C.
, Finegold
M.
, Hou
H.
, Thompson
J. C.
, Silverman
A.
, Harper
J. W.
, DePinho
R. A.
, Elledge
S. J.
(1997
) Altered cell differentiation in mice lacking p57 KIP2 indicates a role in Beckwith-Wiedemann syndrome.
Nature
387
, 151
–158
This content is only available via PDF.
© 1998 by Company of Biologists
1998
-JournalMeeting.png?versionId=3939)
(update)-InPreprints.png?versionId=3939)
-TechniquesAndResources.png?versionId=3939)
(update)-RashmiPriya.png?versionId=3939)
-NodeNetwork.png?versionId=3939)
