These Psen1 knock-out mice exhibit gross skeletal malformations and central nervous system abnormalities with post natal mortality. They are suitable for use in applications related to the study of Alzheimer's disease.
Jie Shen, Harvard Med Sch/Brigham Women's Hosp
Presenilin-1 is the major gene responsible for early-onset familial Alzheimer's disease. Mice that are homozygous null for this gene die within minutes after being born. Externally, mice exhibit shortened tails that curve to the right, thickened necks, loose skin and hind limbs that curve towards the midline. Their weight is 15-20% that of wildtype. Gross skeletal malformations and central nervous system abnormalities are observed. Death presumably results from impaired respiratory mechanics due to ribcage deformities. Histological examination indicates that alveoli are marginally expanded. By embryonic day 9.5, there is a drastic reduction in neural progenitor cells. Later, the brain exhibits hemorrhages and symmetric cerebral cavitation. Cavitation occurs primarily in the ventrolateral region of the ventricular zone in the posterior portion of the brain.
A targeting construct containing a neomycin cassette was electroporated into 129S7/SvEvBrd-derived AB2.1 ES cells. The construct was designed to disrupt exons 2 and 3. ES cells were injected into C57BL/6 blastocysts. Resulting animals were crossed to C57BL/6. The mutation generates aberrant mRNA splice products; no protein is detected.
|Allele Name||targeted mutation 1, Jie Shen|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Psen1, presenilin 1|
|Gene Synonym(s)||AD3; Ad3h; Ad3h; FAD; PS-1; PS1; S182; alzheimer disease 3 homolog; presenilin-1|
|Strain of Origin||129S7/SvEvBrd-Hprt |
|Molecular Note||Exon 3 of the Psen1 gene, encoding the translation initiation codon, was deleted and replaced with a neomycin cassette. Northern blots of brain tissue from homozygous mutant mice showed a small amount of mutant Psen1 mRNA, smaller in size than wild-type Psen1. IP-Western blotting detected no C-terminal protein fragment in homozygous mutant mice. The authors conclude that this mutant is a null allele.|
|Mutations Made By|| |
Jie Shen, Harvard Med Sch/Brigham Women's Hosp
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