Sci. Aging Knowl. Environ., 25 September 2002
Vol. 2002, Issue 38, p. tg9
GENETICALLY ALTERED MICE
Harlequin (Hq) Mice
||The mutation initially appeared in a CF1 outbred stock. The mutation was transferred to B6CBACa-Aw-J/A-Hq mice from The Jackson Laboratory, which were mice of a mixed background (C57Bl/6 and CBA) maintained by sibling mating.
||Apoptosis-inducing factor (AIF)
|Type of change
||Ecotopic proviral insertion into intron 1 of the gene, leading to an 80% reduction in protein expression.
|Nature of protein
||AIF is a flavoprotein normally confined to the intermembrane space of the mitochondrion, where, in certain brain and retinal neurons, it acts as a free radical scavenger. Because these mice produce only a small amout of AIF, their neurons undergo oxidative stress. In cells treated with an apoptotic stimulus, AIF translocates to the nucleus, inducing chromatin condensation and DNA cleavage.
||Hemizygous males and homozygous females are nearly hairless, weigh less than normal, and develop ataxia by 5 months of age. In hemizygous males, the ataxia progresses to a severe state and is associated with cerebellar cortical atrophy and extensive loss of Purkinje and granule cells. These mice constitute a genetic model of neurodegeneration caused by oxidative stress.
|Corresponding human phenotype
||J. A. Klein, C. M. Longo-Guess, M. P. Rossman, L. Seburn, R. E. Hurd, W. N. Frankel, R. T. Bronson, S. L. Ackerman, The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature 419, 367-374 (2002).
||Harlequin mice (stock number 000501) are commercially available through the Jackson Laboratory (http://jaxmice.jax.org).
||ataxia, hairless, apoptosis, apoptosis-inducing factor
September 25, 2002
- B. R. Barber, Two new mutations. Mouse News Lett. 45, 34-35 (1971).
- R. T. Bronson, P. W. Lane, B. S. Harris, M. T. Davisson, Harlequin (Hq) produces progressive cerebellar cortical atrophy. Mouse Genome 87, 110-117 (1990).
- D. S. Falconer, J. H. Isaacson, Harlequin and Brindled- Linkage and difference between coupling and repulsion phenotypes. Mouse News Lett. 47, 28 (1972).
- J. A. Klein, C. M. Longo-Guess, M. P. Rossman, L. Seburn, R. E. Hurd, W. N. Frankel, R. T. Bronson, S. L. Ackerman, The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature 419, 367-374 (2002).[CrossRef][Medline]
Harlequin (Hq) Mice. Science's SAGE KE
(25 September 2002), http://sageke.sciencemag.org/cgi/content/full/sageke;2002/38/tg9