Modification: PSEN2: Knock-Out
Disease Relevance: Alzheimer's Disease
Strain Name: B6.129P-Psen2tm1Bdes/J
Genetic Background: 129P2/OlaHsd derived embryonic stem cells injected into C57BL/6 blastocysts; resulting chimeric mice backcrossed to C57BL/6J
Availability: The Jackson Lab: Stock# 005617; Cryopreserved
These mice lack PSEN2; no gene product (mRNA or protein) is detected by Northern or Western blot analysis. Homozygous mice are viable, born at expected Mendelian frequency, and fertile. They are normal in growth and size and do not display any gross physical or behavioral abnormalities up to twelve months of age. They have no gross brain abnormalities or astrogliosis relative to wild-type controls. They do develop an age-associated lung phenotype, specifically from age three months PSEN2 knock-out animals develop considerable alveolar wall thickening with fibrosis and hemorrhages in alveoli around three to six months. APP processing does not appear to be affected (Herreman et al., 1999).
A targeting vector containing a neomycin resistance gene was inserted downstream of exon 7 of PSEN1; loxP sites were inserted on both sides of exon 7 and downstream of the neomycin resistance gene.
Last Updated: 16 Aug 2013
- 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. PubMed.
- Yun HM, Park MH, Kim DH, Ahn YJ, Park KR, Kim TM, Yun NY, Jung YS, Hwang DY, Yoon DY, Han SB, Hong JT. Loss of presenilin 2 is associated with increased iPLA2 activity and lung tumor development. Oncogene. 2014 Oct 30;33(44):5193-200. Epub 2014 May 26 PubMed.