cDNA construction: The mosue PS2 cDNA was provided by L. D'Adamio (National
Institutes of Health). An EMBL3-129 SV Mouse genomic phage library was screened,
and phage 7 containing a 15 kb insert including exon 4 was used to generate the
Mice construction: PS2 gene was inactivated by homologous recombination. Exon
5 of the mouse PS2 gene in E14-1 ES cells was replaced by a hygromycin cassette
under the control of the PGK promoter. The replacement of exon 5 results in a frameshift
between exons 4 and 6.
Background: Two independently targeted ES clones were microinjected into C57BL/6J
balstocysts, and chimeric males and heterozygous offspring were generated. C57B6/J
black x 129Sv genetic background used.
Disruption of the PS2 gene does not result in embryonic letality, in contrast to
PS1-/-. PS2 homozygous mutant, heterozygous, and wt mice resulting from heterozygote
corsses did not exhibit obvious differences in growth, weight, or health up to age
PS2-deficient mice were fertile. Various blood and serum parameters revealed no
Detailed microscopic examination of brain (hippocampus as a key target region),
liver, spleen, heart, and skeletal muscle did not reveal any abnormalities in tissue
structure or indirect evidence of lesions.
From age 3 months on, PS2-/- mice displayed a considerable thickening of alveolar
walls, with broad strands of fibrotic tissues. Age 3 and 6 months, hemorrhages observed
within large groups of alveoli and their adjoining airways. However, transgenic
mice suffered very little from these fibrotic alterations.
The lack of PS2 gene in mice does not result in an obvious phenotype.
The Jackson Lab,
cryopreserved, stock #005617. Use by companies or for-profit entities requires a
license prior to shipping.
Herreman A, Hartmann D, Annaert W, Saftig P, Craessaerts K, Serneels L, Umans L,
Schrijvers V, Checler F, Vanderstichele H, Baekelandt V, Dressel R, Cupers P, Huylebroeck
D, Zwijsen A, Van Leuven F, De Strooper B. Presenilin 2 deficiency causes a mild
pulmonary phenotype and no changes in amyloid precursor protein processing but enhances
the embryonic lethal phenotype of presenilin 1 deficiency. Proc Natl Acad Sci U
S A 1999 Oct 12;96(21):11872-7.