DETAILED DESCRIPTION What is claimed is: 1.
A nematode having null mutations in hop-1 and sel-12, said nematode having a combined maternal-effect embryonic lethality and egg laying defective phenotype, at least one of said mutations being introduced by artifice, wherein said nematode is a C.
elegans nematode.
Description:
BACKGROUND OF THE INVENTION The field of the invention is Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system involving loss of memory and cognitive function.
Neuropathological hallmarks of AD extracellular amyloid plaques, whose major component is the A.
beta.
peptide, a proteolytic product of the .
beta.
-amyloid precursor protein (APP).
Dominant mutations in any of three mammalian genes, PS1, PS2, and APP are causative for the early-onset, familial form of AD (FAD).
PS1 and PS2 encode related proteins-, while APP encodes the amyloid precursor protein (APP) (reviewed in Hardy, Trends Neurosci.
20:154-159, 1997), from which the A.
beta.
peptide is generated by proteolytic processing.
Since presenilin-1 (PS1) and presenilin-2 (PS2) were first identified as genes mutated in FAD, much effort has been devoted to elucidating the biological function of presenilins in normal and disease states.
Two lines of evidence support a hypothesis that presenilins affect proteolytic processing of APP First, PS(FAD) mutations are associated with an increase in a longer, more amyloidogenic form of A.
beta.
known as A.
beta.
42 ; and second, levels of A.
beta.
are decreased several-fold in neurons derived from PS1 knockout mice relative to PS1(+) control mice.
Moreover, in neurons, A.
beta.
42 may be generated in the endoplasmic reticulum, where presenilins have been localized.
C.
elegans has three presenilin genes, spe-4 (spermatogenesis defective) (L'Hernault, et al.
, J.
Cell Biol.
, 119:55-68, 1992), sel-12 (suppressor and/or enhancer of lin-12) (Levitan et al.
, Nature 377:351-354, 1995), and hop-1 (homolog of presenilin) (Li et al
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Gene Therapy 
