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Thread: Mouse created without father - first mouse parthenogenesis - implications for spinal cord injury

  1. #1

    Mouse created without father - first mouse parthenogenesis - implications for spinal cord injury

    This is a really interesting and important discovery. The authors from Tokyo University of Agriculture successfully produced mice by combining two eggs, one of which expresses a gene called H19 and the other expresses Igf2. The headlines of course emphasize the sensational aspect of this work, i.e. "mouse created without father", "the mouse that roared: Virgin Birth"... People are talking about lesbians being able to have babies...

    But the real scientific story behind this achievement is much deeper and has significance for stem cell research, cloning, and hence spinal cord injury. What these scientists discovered was the mechanism by which mammals prevent parthenogenesis. For a long time, scientists have known that there is something that a mammalian sperm brings to a mammalian egg that allows it to produce a viable organism.

    So what, you ask. Any 10 year old could have told you that a father is necessary for a baby from the mother. But, why can all submammalian species produce by parthenogenesis (a process whereby one can fool an egg into thinking that it has been fertilized, to produce a fetus) and mammals cannot. Well, as it turns out, the mammalian egg and mammalian sperm have different sets of genes turned on and off. Both male and female mice have both H19 and Igf2 genes. However, in the egg, H19 is turned on but a gene called Igf2 is turned off. In sperm, the opposite is true: Igf2 is turned on and H19 is turned off. These two genes are next door to each other. It turns out that Igf2 is necessary for the blastocyst (the little ball that contains stem cells) to implant and develop into the amniotic sac and other tissues that support the growth of the fetus. H19 turns out to be critical for the growth of the fetus.

    It is possible to fool a mammalian egg to start dividing but, without Igf2, the blastocyst tends to stop growing and will not support further fetal development. What Kono, et al. did was to produce a strain of mice that express Igf2 from another site of the genome (i.e. that was not turned off in the egg). They then took the nucleus from this mouse and transfered it into an egg from a regular mouse that expressed H19 but not IgF2. When they then activated the egg, it produced blastocysts that could be implanted and several developed to form apparently normal and fertile female mice.

    A careful perusal of the paper indicated that the authors started with a total 598 combined eggs. They artificially activated these eggs and 457 (78%) of these activated eggs started to divide. Of these, 371 (91.2%) produced blastulas which are little balls containing stem cells. They transferred these into 26 female mice (14-15 eggs per female) and 24 of the mice became pregnant. They then killed the mice and removed the embryos at 19.5 days of gestation. They found 10 live and 19 dead pups, and succcessfully restored two of the live pups. One of these grew to adulthood and appeared to be normal and fertile.

    While getting one living adult mouse from 598 eggs seems to be very inefficient, they were able to get 91% of the original eggs to produce blastocysts that contain stem cells. This is a very high yield indeed. When W. S. Huang from Korea produced the first cloned human embryonic stem cells, he began with over 200 eggs to generate 40 blastocysts, less than 20% success rate, and this was considered to be very good. Combining two eggs is five times more efficient at producing blastocysts than somatic nuclear transfer.

    So, now, in the last 3 months, the efficiency of producing blastocysts has increased by more than an order of magnitude. Here is now a method that is successful over 90% of the time in producing blastocysts. If this method can be applied to humans with similar probabilities of creating viable blastocysts, there is a reasonable chance that this could be done with perhaps 10 eggs. This is well within the number of eggs that can be obtained from a woman in a single egg-gathering procedure for in vitro fertilization.

    Note that this procedure is technically not somatic cell nuclear transfer. It is not even "cloning" because the parthenote had genes from two female mice). Thus, this approach provides a relatively efficient method of producing human embryonic stem cells while circumventing the restrictions on cloning and somatic cell nuclear transfer. Of course, some additional developments may be needed to get a parthenote that has the genes of a man... But, this study now presents the theoretical possibility for women to have stem cells that contain their own genes by donating a reasonably small number of eggs and combining them. What seemed impossible just a few months ago is now high probable.

    Wise.



    http://www.nature.com/nsu/040419/040419-8.html

    Mouse created without father
    Scientists turn egg cell into surrogate sperm.
    22 April 2004

    HELEN PEARSON

    Kaguya is one sucess from 460 attempts at growing embryos.


    テつゥ T. Kono

    From time immemorial, making a mammalian baby has involved two essential ingredients: eggs and sperm. Now Japanese scientists have written men out of the reproduction rule-book, and created fatherless mice.

    The team made the animals by combining the nucleus of one female's egg with that of another, essentially creating a mouse with two mothers. "It is a bit of a surprise," says evolutionary biologist David Haig of Harvard University, Boston.

    After nearly 460 attempts at growing embryos, ten live pups were born and just one of those survived to adulthood. Christened Kaguya, from the story of a girl discovered in a bamboo stump, the mouse is now 14 months old and has babies of her own. She is "very healthy", says team leader Tomohiro Kono of Tokyo University of Agriculture. ...
    The original article is at Nature 428, 860-864 (22 April 2004)

    Nature 428, 860 - 864 (22 April 2004); doi:10.1038/nature02402

    Birth of parthenogenetic mice that can develop to adulthood

    TOMOHIROテつ*KONO1,3, YAYOIテつ*OBATA1,3, QUIONGテつ*WU1,3, KATSUTOSHIテつ*NIWA1,3, YUKIKOテつ*ONO1, YUJIテつ*YAMAMOTO2,3, EUNテつ*SUNGテつ*PARK4, JEONG-SUNテつ*SEO4,5 & HIDEHIKOテつ*OGAWA1,3

    1テつ*Department of BioScience, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan
    2テつ*Department of Applied Science, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan
    3テつ*Bio-oriented Technology Research Advancement Institution (BRAIN), Minato-ku, Tokyo 105-0001, Japan
    4テつ*MacroGen Inc, Chongno-Ku, Seoul 110-061, Korea
    5テつ*Department of Biochemistry, Seoul National University College of Medicine, Chongno-Ku, Seoul 110-799, Korea

    Correspondence and requests for materials should be addressed to T.K. (tomohiro@nodai.ac.jp).

    Only mammals have relinquished parthenogenesis, a means of producing descendants solely from maternal germ cells. Mouse parthenogenetic embryos die by day 10 of gestation. Bi-parental reproduction is necessary because of parent-specific epigenetic modification of the genome during gametogenesis. This leads to unequal expression of imprinted genes from the maternal and paternal alleles. However, there is no direct evidence that genomic imprinting is the only barrier to parthenogenetic development. Here we show the development of a viable parthenogenetic mouse individual from a reconstructed oocyte containing two haploid sets of maternal genome, derived from non-growing and fully grown oocytes. This development was made possible by the appropriate expression of the Igf2 and H19 genes with other imprinted genes, using mutant mice with a 13-kilobase deletion in the H19 gene as non-growing oocytes donors. This full-term development is associated with a marked reduction in aberrantly expressed genes. The parthenote developed to adulthood with the ability to reproduce offspring. These results suggest that paternal imprinting prevents parthenogenesis, ensuring that the paternal contribution is obligatory for the descendant.
    [This message was edited by Wise Young on 04-22-04 at 06:32 AM.]

  2. #2
    Senior Member Schmeky's Avatar
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    Dr. Young,

    This truly is a remarkable development, much akin to science fiction.

    The ONLY drawback I see, is that men may be obsolete in the future!!

  3. #3
    Good news! lots of stem cells, bad news! men are no longer needed. Doc does this mean the end of Father's Day? or will they keep us around as a boy toy!

    How soon could this double/egger help the supply for ESC research?

  4. #4

  5. #5
    whoops, I just realized that I said "mouse created with father..." in the headlines. Sigh. Comes from typing too quickly and not proof-reading.

    In thinking about this, it is really unfortunate the the authors of this study chose to expend the blastocysts by implanting them and trying to get an adult mouse when, in reality, the much more important finding is that they have created the first efficient way to produce parthenogetic embryonic stem cells without the haploid problem (single set of chromosomes), without technically doing somatic nuclear transfer, and without evening "cloning". Because they went ahead to produce an adult offspring, this raises the hackles of people who are against cloning and this may end up with the banning of this approach towards creating stem cells. That would be sad.

    Wise.

  6. #6
    Originally posted by EAA:

    ..., bad news! men are no longer needed. Doc does this mean the end of Father's Day? or will they keep us around as a boy toy!
    Not only that, but the world would soon be populated by females only, since there is no chromosome Y involved in producing that baby..

  7. #7
    Lel, clearly nature has gone to quite a lot of trouble to prevent parthenogenesis in mammals. If one believes in evolution, this would imply that parthenogenesis has a serious disadvantage for survival in mammals.

    The question is why submammalian species allow parthenogenesis. Perhaps this is because there are times when the number of a particular species gets to such a low point that parthenogenesis is useful for survival of the species.

    Wise.

  8. #8
    Senior Member kilgore's Avatar
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    First, there was a bill in Wisconsin that expressly prohibited cloning AND parthenogenesis. Fortunately, it failed last month (due to a year of inactivity), but it shows that conservatives won't let this research slip by unnoticed.

    Second, I've done a lot in my life, but haven't produced any eggs. Maybe I'm just not trying hard enough. Is there a way to apply the technology to another type of cell?

  9. #9
    Originally posted by Wise Young:

    Lel, clearly nature has gone to quite a lot of trouble to prevent parthenogenesis in mammals. If one believes in evolution, this would imply that parthenogenesis has a serious disadvantage for survival in mammals.
    Dr. Young, I was making a litle joke out of it...
    I don't think our society is ready to accept parthenogenesis as a normal way of producing offspring.

    The question is why submammalian species allow parthenogenesis.

    Doesn't that have to do with their genetics? Why submmamalians have unfertilised eggs with two sets of chromosomes which develop as if they had been fertilized,and mammals don't? Don't ask me on that, ask mother nature..

    Perhaps this is because there are times when the number of a particular species gets to such a low point that parthenogenesis is useful for survival of the species.
    Perhaps...!

    [This message was edited by lel42 on 04-30-04 at 11:08 AM.]

  10. #10
    Senior Member DA's Avatar
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    Originally posted by Schmeky:

    Dr. Young,

    This truly is a remarkable development, much akin to science fiction.

    The ONLY drawback I see, is that men may be obsolete in the future!!
    it may hurt womens rights and standard of living. women will be put in charge of kids, men free to be free. no child support, nothing.

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