Cloning of mice to six generations

Wakayama, Teruhiko; Shinkai, Yoichi; Tamashiro, Kellie L.K.; Niida, Hiroyuki; Blanchard, D. Caroline; Blanchard, Robert J.; Ogura, Atsuo; Tanemura, Kentaro; Tachibana, Makoto; Perry, Anthony C.F.; Colgan, Diana F.; Mombaerts, Peter; Yanagimachi, Ryuzo

doi:10.1038/35030301

Cited by 210 publications

(143 citation statements)

References 8 publications

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“…Notably, the pregnancy success rate after four rounds of fetal serial cloning was as high as 71%; however, the efficiency for term development is not yet known. The discrepancy between this study and previous serial cloning reports 9,10 , which found progressive decreases in cloning efficiency, is probably due to the different source of donor cells (adult versus fetal cells).…”

Section: N E W S a N D V I E W Scontrasting

confidence: 99%

“…Cell rejuvenation in clones by rebuilding of eroded telomeres from aged donor cells in cattle 7,8 has been confirmed previously. Telomere reprogramming has also been found after serial cloning in cattle 9 and mice 10 . Notably, the pregnancy success rate after four rounds of fetal serial cloning was as high as 71%; however, the efficiency for term development is not yet known.…”

Section: N E W S a N D V I E W Smentioning

confidence: 92%

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Cattle call for gene targeting

2004

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The discovery that a differentiated somatic cell can give rise to a new organism through nuclear transfer cloning touched off a revolution in genetics. A new study outlining how to target genes serially in cows ushers in a new era in large-animal genetics. N E W S A N D V I E W SNATURE GENETICS VOLUME 36 | NUMBER 7 | JULY 2004 671Somatic cell cloning involves replacing the nucleus of an oocyte with that of a somatic cell, which then directs development of the reconstructed embryo into a new organism with a nuclear genome identical to that of the donor cell 1 . Cloning using somatic cells cultured long-term 2 laid the foundation for single-gene targeting in species other than mouse 3 . But targeting multiple genes by cloning has not been possible because of the limited lifespan of primary somatic cells and the long gestational times of large animals. The paper by Yoshimi Kuroiwa and colleagues 4 on page 775 reports a sequential targeting technique that integrates homologous recombination, positive and negative selection, and Cre-loxP recombination with serial cloning to rejuvenate somatic cells and facilitate modification of multiple genes in a single cloned animal (Fig. 1a). Rejuvenation by serial cloningGenerating a homozygous single-gene knockout cow would take ∼6 years using conventional methods (Fig. 1b). First, a gene of interest would be knocked out by homologous recombination in cultured somatic cells (typically fibroblasts), which would then be cloned to create a heterozygous calf with a targeted mutation. The heterozygotes would be raised to maturity for breeding (∼2 years of age) to generate first-generation (F 1 ) male and female heterozygous calves, which would be crossbred to generate a homozygous knockout calf. Generating homozygotes with respect to multiple targeted mutations using the conventional approach in cattle would be impractical. In contrast, the sequential targeting strategy described by Kuroiwa et al. makes multiple genetic modifications in cattle, allowing the generation of homozygous cows in less than 2 years (Fig. 1a). First, the targeted cloned embryos are transferred to foster mothers to generate fetuses (not for term development, but for rejuvenating somatic cells for the next round of gene targeting). The rejuvenated fetal cells are then collected and subjected to a second round of homologous recombination

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Section: N E W S a N D V I E W Scontrasting

confidence: 99%

Section: N E W S a N D V I E W Smentioning

confidence: 92%

Cattle call for gene targeting

2004

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“…For example, by applying restriction landmark genome scanning (RLGS) in two seemingly healthy cloned mice, it was shown that methylation patterns at several sites in each clone differed from those in the controls (Ohgane et al, 2001). It should be emphasized, however, that reprogramming that occurs postzygotically such as X-chromosome re-activation and subsequent inactivation (Eggan et al, 2000) and telomere length adjustment (Lanza et al, 2000a;Tian et al, 2000;Wakayama et al, 2000a;Betts et al, 2001) are faithfully accomplished in apparently normal cloned embryos. Nevertheless, X inactivation errors and chromosomal aberrations have been seen in visibly abnormal cloned embryos (Xue et al, 2002;Nolen et al, 2005).…”

Section: Dna Methylation and Ntmentioning

confidence: 99%

Mammalian nuclear transfer

Meissner

Jaenisch

2006

Developmental Dynamics

112

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During development, the genetic content of each cell remains, with a few exceptions, identical to that of the zygote. Differentiated cells, therefore, retain all the genetic information necessary to generate an entire organism (nuclear totipotency). Nuclear transfer (NT) was initially developed to test experimentally this concept by cloning animals from differentiated cells. It has, since then, been used to study the role of genetic and epigenetic alterations during development and disease. In this review, we highlight some of the milestones in mammalian NT reached in the 50 years after the first nuclear transplantations in frogs. We also address problems associated with mammalian nuclear transfer and provide a survey on current NT and stem cell technology. In the long term, nuclear transfer or alternative strategies aim to generate customized pluripotent cells, which would be invaluable to medical research and therapy. Developmental Dynamics 235: 2460 -2469, 2006.

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“…Another measure of reprogramming of somatic nuclei is the potential to restore the telomere size and to overcome senescence [65][66][67][68] . Although there is some evidence that telomere length is restored in somatic nuclei after transplantation into oocytes, most DNA mutations in the somatic nucleus cannot be repaired.…”

Section: Reprogramming Somatic Nuclei In the Oocytementioning

confidence: 99%

Reprogramming of genome function through epigenetic inheritance

Surani

2001

Nature

411

296

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Most cells contain the same set of genes and yet they are extremely diverse in appearance and functions. It is the selective expression and repression of genes that determines the specific properties of individual cells. Nevertheless, even when fully differentiated, any cell can potentially be reprogrammed back to totipotency, which in turn results in re-differentiation of the full repertoire of adult cells from a single original cell of any kind. Mechanisms that regulate this exceptional genomic plasticity and the state of totipotency are being unravelled, and will enhance our ability to manipulate stem cells for therapeutic purposes.

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Cloning of mice to six generations

Cited by 210 publications

References 8 publications

Cattle call for gene targeting

Cattle call for gene targeting

Mammalian nuclear transfer

Reprogramming of genome function through epigenetic inheritance

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