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Title: The biology of novel animal genes: Mouse APEX gene knockout

This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The controlled breeding of novel genes into mice, including the gene knockout (KO), or conversely by adding back transgenes provide powerful genetic technologies that together suffice to determine in large part the biological role(s) of novel genes. Inbred mouse remains the best understood and most useful mammalian experimental system available for tackling the biology of novel genes. The major mammalian apurinic/apyrimidinic (AP) endonuclease (APE), is involved in a key step in the repair of spontaneous and induced AP sites in DNA. Efficient repair of these lesions is imperative to prevent the stable incorporation of mutations into the cellular genome which may lead to cell death or transformation. Loss or modulation of base excison repair activity in vivo may elevate the spontaneous mutation rate in cells, and may lead to a substantial increase in the incidence of cancer. Despite extensive biochemical analysis, however, the significance of these individual APE functions in vivo has not been elucidated. Mouse embryonic stem (ES) cells heterozygous for a deletion mutation in APE have been generated and whole animals containing the APE mutation havemore » been derived from these ES cells. Animals homozygous for the APE null mutation die early in gestation, underscoring the biological significance of this DNA repair gene.« less
Authors:
; ;  [1] ; ;  [2]
  1. Los Alamos National Lab., NM (United States)
  2. Univ. of California, San Francisco, CA (United States)
Publication Date:
OSTI Identifier:
505320
Report Number(s):
LA-UR--97-1517
ON: DE97007837; TRN: AHC29716%%72
DOE Contract Number:
W-7405-ENG-36
Resource Type:
Technical Report
Resource Relation:
Other Information: PBD: [1997]
Research Org:
Los Alamos National Lab., NM (United States)
Sponsoring Org:
USDOE Assistant Secretary for Human Resources and Administration, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; DNA REPAIR; GENES; ENDONUCLEASES; TRANSGENIC MICE; GENE MUTATIONS; BIOLOGICAL FUNCTIONS