Sci. Aging Knowl. Environ., 9 March 2005
Vol. 2005, Issue 10, p. tg2
GENETICALLY ALTERED MICE
||129S4/SvJaeSor (embryonic stem cells), C57BL/6 (blastocysts)
||parkin; also called PRKN and Park2
|Type of change
||Targeted deletion of parkin (Park2) exon 2 (which encodes most of the ubiquitin-like domain) was achieved by homologous recombination. This manipulation is also predicted to result in a frame shift if exons 1 and 3 are spliced together.
|Nature of protein
||Parkin protein is characterized by a ubiquitin-like domain at its N terminus and two RING finger motifs and an IBR ("in between RING fingers") region at its C terminus. Parkin is a RING-type E3 ubiquitin-protein ligase that binds to E2 ubiquitin-conjugating enzymes, including ubiquitin-conjugating human enzyme 7 (UbcH7) and UbcH8 (see Gray Review).
||Aged Park2tm1Rpa mice are essentially like wild-type genetically matched controls and demonstrate none of the deficiencies in neurological function, emotionality, learning, or memory that have been reported in studies using Parkin-deficient mice generated by others.
|Corresponding human phenotype
||Autosomal recessive juvenile parkinsonism is caused by mutations in the parkin gene. A study of families with early-onset Parkinson's disease (PD) (beginning before age 45) showed that almost half had PARK2 mutations. The average age at onset of PD in the patients with PARK2 mutations was earlier than in those without mutations; those with mutations were more likely to have symmetric involvement and dystonia (abnormal tonicity of muscle) at onset.
See Constantino Case Study for a description of a patient with PD.
||F. A. Perez, R. D. Palmiter, Parkin-deficient mice are not a robust model of parkinsonism. Proc. Natl. Acad. Sci. U.S.A. 102, 2174-2179 (2005).
||These mice are not commercially available. Please contact:
Richard D. Palmiter
Department of Biochemistry
Howard Hughes Medical Institute
University of Washington
Health Sciences Building, Room J661D
Seattle, WA 98195
||Parkin-deficient mice, as described in other studies, exhibit disrupted dopamine and glutatamate transmission, resulting in neurological deficits, including decreased exploratory behavior. Furthermore, these mice display reduced body weight and body temperature as compared to the wild type. Inconsistencies between the phenotypes of Park2tm1Rpa mice and other Parkin-deficient mice might occur because of (i) differences in genetic background, (ii) differences in parkin mutations, or (iii) artifacts caused by gene targeting.
||Mouse Gene Informatics (includes summaries of other Parkin-deficient mice):
Online Mendelian Inheritance in Man:
SAGE KE's Genes/Interventions database:
E3 ubiquitin-protein ligase
March 9, 2005
- K. Kuhn, X. R. Zhu, H. Lubbert, C. C. Stichel, Parkin expression in the developing mouse. Brain Res. Dev. Brain Res. 149, 131-142 (2004).[CrossRef][Medline]
- C. B. Lucking, A. Durr, V. Bonifati, J. Vaughan, G. De Michele, T. Gasser, B. S. Harhangi, G. Meco, P. Denefle, N. W. Wood, et al., Association between early-onset Parkinson's disease and mutations in the parkin gene. N. Engl. J. Med. 342, 1560-1567 (2000).[CrossRef][Medline]
- F. A. Perez, R. D. Palmiter, Parkin-deficient mice are not a robust model of parkinsonism. Proc. Natl. Acad. Sci. U.S.A. 102, 2174-2179 (2005).[Abstract/Free Full Text]
- R. Von Coelln, B. Thomas, J. M. Savitt, K. L. Lim, M. Sasaki, E. J. Hess, V. L. Dawson, T. M. Dawson, Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc. Natl. Acad. Sci. U.S.A. 101, 10744-10749 (2004).[Abstract/Free Full Text]
Mice. Sci. Aging Knowl. Environ. 2005
(10), tg2 (2005).