Posted 6 March 2005

General Information

Transgene: The Hq allele of Pdcd8 has a murine ecotropic proviral insertion in intron 1 beginning at genomic base pair 3432. Chromosome X.

Mutation: Spontaneous

Mouse strain: B6CBACa A^w-J/A-Pdcd8^Hq/J

Phenotype

Neuropathological analysis

Genetic model of oxidative stress-mediated neurodegeneration. Progressive degeneration of terminally differentiated cerebellar and retinal neurons. AIF (apoptosis inducing factor) expression is reduced by 80%. Ataxia is noticeable by 5 months and progresses as the mice age. A delayed cerebellar cortical atrophy with an apoptotic loss of granule cells beginning at 4 months and a necrotic loss of Purkinje cells occurring subsequently. The granule cells re-enter the cell cycle, but the Purkinje cells do not.

Crosses

Harlequin crossed with Apaf1-/- mice (Cheung, 2004).
Harlequin crossed with Tg (βA-G11PLAP) (Stringer, 2004).

Behavioral

Hemizygous males, homozygous females and hemizygous females are all viable and fertile.

Availability

Licensing/academic distribution contact information:

Available: The Jackson Lab: #000501

Patents: None

References

Primary:

Klein JA, Longo-Guess CM, Rossmann MP, Seburn KL, Hurd RE, Frankel WN, Bronson RT, Ackerman SL.The harlequin mouse mutation down regulates apoptosis-inducing factor. Nature 2002 Sep 26; 419(6905): 367-74. Abstract

Associated:

Cheung EC, Melanson-Drapeau L, Cregan SP, Vanderluit JL, Ferguson KL, McIntosh WC, Park DS, Bennett SA, Slack RS. Apoptosis-inducing factor is a key factor in neuronal cell death propagated by BAX-dependent and BAX-independent mechanisms. J Neurosci. 2005 Feb 9; 25(6): 1324-34. Abstract

Stringer JR, Larson JS, Fischer JM, Stringer SL. Increased mutation in mice genetically predisposed to oxidative damage in the brain. Mutat Res. 2004 Nov 22; 556(1-2): 127-34. Abstract