NDLI: Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice.

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Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kim, H. S. Smithies, O.
Description	Author Affiliation: Smithies O ( Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.);
Abstract	Experimental analysis of complex quantitative genetic traits, such as essential hypertension, should be greatly facilitated by being able to manipulate the expression of a gene in living animals without altering the nucleotide sequence, chromosomal location, or regulatory elements of the gene. To explore this possibility, we have used targeted gene disruption and duplication to generate mice that are genetically identical [(129 x C57BL6)F1] except for having one, two, or three functional copies of the gene coding for angiotensinogen. The two-copy animals have two normal copies of the angiotensinogen gene; the one-copy and three-copy animals have one normal copy with the other either disrupted or duplicated by gene targeting. The duplicated pair of genes was generated by a special form of gap-repair gene targeting that tandemly duplicates the whole of a gene together with 5' and 3' flanking regions. We find progressively and significantly higher levels of the gene product in the animals having increasing numbers of gene copies: the one-copy animals have steady-state plasma angiotensinogen levels approximately 35% of normal (P < 0.0001), and the three-copy animals have levels approximately 124% of normal (P < 0.004). Detailed information about regulatory sequences is not required for this type of experiment; nor is it necessary to have DNA clones or targeting constructs that cover the whole of the target gene. Varying gene copy numbers by targeting consequently offers a promising approach to quantitative genetics.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	91
Language	English
Publisher	National Academy of Sciences
Publisher Date	1994-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Angiotensinogen Genetics Multigene Family Animals DNA Primers Chemistry DNA Repair Gene Expression Hypertension Mice Mice, Knockout Molecular Sequence Data Restriction Mapping Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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