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gene knockouts

Mark D. Garfinkel garfinkl at iitmax.iit.edu
Thu Jun 2 15:46:10 EST 1994

tme9u at galen.med.Virginia.EDU (teresa m. esch) writes:

>I was just wondering about whether anyone has studied the
>effect of gene knockouts on selective advantage.  Since it
>seems that so many gene knockouts have apparently trivial
>effects on development and physiology, at least for nervous
>system genes, [...]
	I'm not sure which "knockouts" you're talking about. Every mouse
strain that arises from Cappechi et al. style disruption of Cloned Gene X
has a homozygous-recessive phenotype worthy of publication in Cell or
Science. Since each such strain takes nearly a year and $25-50K to
produce, they darned-well better have Cell-grade properties! Agreed that
many are neonatal-lethal rather than embryo- or fetal-lethal, and perhaps
that is surprising. Partly redundant functions by other members of the gene
family is the typical explanation, which may be a crock. But a homozygous-
mutant phenotype involving serious anatomical malformation and death prior
to sexual maturity seems like a non-trivial, strongly disadvantageous
phenotype. At least to me.

>I was wondering what would happen if you raised
>knockout animals, probably fruit flies, along with wild type in
>a "natural" environment, and check after many generations to
>see whether the wild type actually have an advantage
>over the knockout [...]
	This experiment has been done, in effect, by different methods
in very many cases with the fly. What you call a knockout, imprecisely
I might add, is more properly called a null allele. And many of the
genes coding for "highly conserved and therefore presumably important
proteins," as you called them, are mutable to a recessive-lethal null
phenotype. This was how many of them were identified in the first place.
As above, death is a strongly disadvantageous homozygous-recessive
phenotype; accordingly Drosophila geneticists long ago devised special
balanced-heterozygous chromosome segregation tools to facilitate
maintenance of recessive-lethal mutations in lab stocks.

Mark D. Garfinkel (e-mail: garfinkl at iitmax.acc.iit.edu)
My views are my own, which is why they're copyright (c) 1994

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