Posted 28 January 2005
Transgene: Developed a floxed PS1 mouse (PS1 exons 2 and 3 are
flanked by two loxP sites) (Yu et al., 2000 and 2001), crossed with Nestin-Cre
transgenic mice (Tronche et al., 1999) to obtain mice heterozygous for the
fPS1 allele and hemizygous for the Nestin-Cre allele, then crossed
with fPS1/fPS1 mice to obtain PS1 cKO (fPS1/fPS1;Nestin-Cre
or fPS1/fPS1Δ;Nestin-Cre) mice. Because PS1 cKO
mice die at 2-3 months of age, they were not ideally suited to be used as breeding
mice. We therefore crossed fPS1/fPS1Δ;Nestin-Cre with fPS1/+
to obtain +/fPS1Δ;Nestin-Cre mice, which were then crossed with
fPS1/fPS1 female mice to obtain fPS1/fPS1Δ;Nestin-Cre
(PS1 cKO) and fPS1/+ (control) mice at a ratio of 1:1, due to
the linkage between the fPS1Δ and Nestin-Cre alleles.
Mutation: CNS-restricted PS1 deletion
Promoter: Nestin promoter
Mouse Strain: B6/129: We have both floxed PS1 and Nestin-Cre
mice that have been backcrossed to B6 for over 12 generations.
Conditional knockout (cKO) mouse in which PS1 inactivation is restricted
to neural progenitor cells (NPCs) and NPC-derived neurons and glia. Neural progenitor
and neuronal populations are greatly reduced, due to premature differentiation of
neural progenitor cells. Generation and survival of Cajal-Retzius (CR) neurons are
unaffected in PS1 cKO mice compared to PS1null mice that show premature
loss. 45% of late-born neurons fail to migrate to their appropriate positions in
the superficial cortical layer while early born neurons are properly positioned
in the deeper cortical layers.
These mice are smaller in size and show many gross behavioral deficits. They can
survive up to 3-4 months of age.
Center for Neurologic Diseases
Brigham and Woman's Hospital
Boston, MA 02115 USA and Program in Neuroscience
Harvard Medical School
Boston, MA 02115 USA
Phone: (617) 525-5561
Fax: (617) 525-5522
Wines-Samuelson M, Handler M, Shen J. Role of presenilin-1 in cortical lamination
and survival of Cajal-Retzius neurons. Dev Biol. 277(2):332-46, 2005.
Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban P, Bock R, Klein R, Schutz
G. Disruption of the glucocorticoid receptor gene in the nervous system results
in reduced anxiety. Nat. Genet. 23:99-103, 1999.
Yu H, Kessler J, Shen J. Heterogeneous populations of Es cells in the generation
of a floxed presenilin-1 allele. Genesis 26:5-8, 2000.
Yu H, Saura CA, Choi S-Y, Sun L D, Yang X, Handler M, Kawarabayashi T, Younkin L,
Fedeles B, Wilson M A, Younkin S, Kandel E R, Kirkwood A, Shen J. APP processing
and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron 31:713-726,