Sci. Aging Knowl. Environ., 7 April 2004
Vol. 2004, Issue 14, p. tg3
[DOI: 10.1126/sageke.2004.14.tg3]

GENETICALLY ALTERED MICE

PARP–/– Mice

http://sageke.sciencemag.org/cgi/content/full/2004/14/tg3


Mouse PARP–/– mice
Genetic background 129SVJ (ES cells), C57BL/6 (blastocysts)
Gene changed PARP [Poly (ADP-ribose) polymerase]; its products are also called Adprt1 (ADP-ribosyltransferase 1); NAD+-poly(ADP-ribose) polymerase 1; Adprp; parp-1; PARP1; and sPARP-1 [short poly(ADP-ribose) polymerase-1].
Type of change Targeted gene disruption.
Nature of protein PARP is a zinc-finger DNA binding protein that detects DNA strand breaks. This enzyme is an adenosine diphosphate (ADP)-ribosyltransferase that functions in the posttranslational modification of nuclear proteins by catalyzing the transfer of ADP-ribose from NAD+ to target proteins (see Vaquero Review), an activity that is greatly enhanced by strand breaks and nicks in DNA.
Phenotype PARP–/– mice are viable and fertile. Studies of the first line of PARP–/– mice to be generated indicated that a high percentage of these mice develop epidermal hyperplasia as they age, although this phenotype was not observed in a different line of PARP–/– mice.
PARP–/– mice appear phenotypically normal except that they weigh approximately 20% less at adulthood than wild-type animals. The litter size of PARP–/– mice is about half that of their wild-type counterparts.
Both embryonic and adult tissues from PARP–/– mice display telomere shortening as compared with tissues from wild-type mice; mouse embryonic fibroblasts that lack PARP exhibit chromosome instability.
Corresponding human phenotype ADPRT activity is reduced or absent in fibroblasts derived from patients with Fanconi anemia, which can be caused by mutations in at least seven different genes. The level of reduction varies depending on the gene affected.
Primary reference Z. Q. Wang, B. Auer, L. Stingl, H. Berghammer, D. Haidacher, M. Schweiger, E. F. Wagner, Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease. Genes Dev. 9, 509-520 (1995).
Additional references See below.
Source These mice are not commercially available. Please contact:
Erwin Friedrich Wagner
Deputy Director, Senior Scientist
Institute of Molecular Pathology (I.M.P.)
Dr. Bohr-Gasse 7
A-1030 Vienna
Austria
E-mail: Wagner{at}imp.univie.ac.at
Keywords ADP-ribosyltransferase
DNA damage
genome stability
telomere shortening
Fanconi anemia
Prepared by Jennifer Fuller


April 7, 2004
  1. F. d'Adda di Fagagna, M. P. Hande, W.-M. Tong, P. M. Lansdorp, Z.-Q. Wang, S. P. Jackson, Functions of poly(ADP-ribose) polymerase in controlling telomere length and chromosomal stability. Nat. Genet. 23, 76-80 (1999).[Medline]
  2. J. Ménissier de Murcia, C. Niedergang, C. Trucco, M. Ricoul, B. Dutrillaux, M. Mark, F. J. Oliver, M. Masson, A. Dierich, M. LeMeur, et al., Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc. Natl. Acad. Sci. U.S.A. 94, 7303-7307 (1997).[Abstract/Free Full Text]
  3. C. M. Simbulan-Rosenthal, B. R. Haddad, D. S. Rosenthal, Z. Weaver, A. Coleman, R. Luo, H. M. Young, Z.-Q. Wang, T. Ried, M. E. Smulson, Chromosomal aberrations in PARP(–/–) mice: genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA. Proc. Natl. Acad. Sci. U.S.A. 96, 13191-13196 (1999).[Abstract/Free Full Text]
  4. M. H. Ramirez, C. Adelfalk, M. Kontou, M. Hirsch-Kauffmann, M. Schweiger, The cellular control enzyme polyADP ribosyl transferase is eliminated in cultured Fanconi anemia fibroblasts at confluency. Biol. Chem. 384, 169-174 (2003).[CrossRef][Medline]
  5. Z. Q. Wang, B. Auer, L. Stingl, H. Berghammer, D. Haidacher, M. Schweiger, E. F. Wagner, Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease. Genes Dev. 9, 509-520 (1995).[Abstract/Free Full Text]
Citation: PARP–/– Mice. Sci. Aging Knowl. Environ. 2004 (14), tg3 (2004).








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