Re: FW: Obesity in mice offers proof of cloning's unpredictability

From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Sun Mar 03 2002 - 00:47:07 MST


On Sun, 3 Mar 2002, Damien Broderick wrote:

> At 09:03 AM 3/1/02 -0800, Robert wrote:
>
> >Actually I think Harvey misses one of the main problems with cloning.
> >The process doesn't get gene imprinting right.
>
> I'm speaking in ignorance of the details, as usual, but this seems
> fallacious. The reset totipotent diploid nucleus would *already* be
> imprinted, surely, and by both parents, from the original conception? Or
> are you arguing that the resetting process strips off the imprint markers
> (which must happen to standard haploid germ cells)?

To be honest Damien, I'm not clear about the details. I'm not even
sure that the people working in the field understand it fully.
I understand what you are saying and it seems to make sense
but I think the devil is in the details. It may be that there
is some strange "struggle" for dominance that occurs in the
developing embryo between the imprinted states. For example
in bacteria, after infection the lambda phage senses whether
the conditions are good for replication -- if not, it enters
a non-reproductive state until things improve. Perhaps the
imprinted genes have similar mechanisms for sensing whether
the mother has the resources to support accelerated growth
and/or determining the priority of the father's or mother's
imprinting.

I do recall reading that the hypothetical purpose for imprinting
of genes like IGF1 was the interests of the father in producing
offspring more likely to survive and the interests of the mother
in preventing the offspring from harming her reproductive capacities.

There may be some interaction between gene imprinting and gene
silencing (as occurs with one copy of the X-chromosome in females).

I think this is still at the level of "theory" and not "proven"
at the practical level.

> >The genes known to be imprinted include Insulin-Like-Growth-Factor-1,
> >I believe, so it isn't surprising that in cloned animals
> >could have problems with obesity.
>
> IGF-1 would be more likely to promote bone and lean muscle growth, no?

IGF1 in adults may have those effects. In developing children it may
serve as a more "general" growth factor (embryos start out with no bones
and no muscles).

This is going to be a very complex area and understanding it completely
is likely to take some time. If you want to know more the best source
would probably be PubMed. Looking up "gene imprinting" and review
should yield what you want.

Robert



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