General Information

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 targeting construct.

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.

Phenotype

Neuropathological analysis:

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 12 months.

PS2-deficient mice were fertile. Various blood and serum parameters revealed no abnormalities.

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.

Behavioral:

The lack of PS2 gene in mice does not result in an obvious phenotype. 

Availability

The Jackson Lab, cryopreserved, stock #005617. Use by companies or for-profit entities requires a license prior to shipping.

Patents: None

Reference

Primary:

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.  Abstract.