Posted 6 March 2005
Transgene: The Hq allele of Pdcd8 has a murine ecotropic proviral
insertion in intron 1 beginning at genomic base pair 3432. Chromosome X.
Mouse strain: B6CBACa Aw-J/A-Pdcd8Hq/J
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
Harlequin crossed with Apaf1-/- mice (Cheung, 2004).
Harlequin crossed with Tg (βA-G11PLAP) (Stringer, 2004).
Hemizygous males, homozygous females and hemizygous females are all viable and fertile.
Licensing/academic distribution contact information:
Available: The Jackson Lab: #000501
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.
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.
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):