Sci. Aging Knowl. Environ., 25 September 2002
Vol. 2002, Issue 38, p. tg9

GENETICALLY ALTERED MICE

Harlequin (Hq) Mice

http://sageke.sciencemag.org/cgi/content/full/sageke;2002/38/tg9


Mouse Harlequin (Hq)
Genetic background 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.
Gene changed 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.
Phenotype 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 None known.
Primary reference 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).
Additional references See below.
Source Harlequin mice (stock number 000501) are commercially available through the Jackson Laboratory (http://jaxmice.jax.org).
Other comments None
Other links None
Keywords ataxia, hairless, apoptosis, apoptosis-inducing factor
Prepared by Galynn Zitnik


September 25, 2002
  1. B. R. Barber, Two new mutations. Mouse News Lett. 45, 34-35 (1971).
  2. 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).
  3. D. S. Falconer, J. H. Isaacson, Harlequin and Brindled- Linkage and difference between coupling and repulsion phenotypes. Mouse News Lett. 47, 28 (1972).
  4. 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]
Citation: Harlequin (Hq) Mice. Science's SAGE KE (25 September 2002), http://sageke.sciencemag.org/cgi/content/full/sageke;2002/38/tg9








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