B6.129-Psen1^tm1Shn/J

Stock number: 003615
Product name: PS1-
Research areas: Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

These Psen1 knock-out mice exhibit a drastic reduction in neural progenitor cells in the embryo with death occuring minutes after being born.

Detailed description

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.

Development

A targeting construct containing a neomycin cassette was electroporated into ES cells. The construct was designed to disrupt exons 2 and 3. ES cells were injected into C57BL/6 blastocysts. Resulting animals generate aberrant mRNA splice products, but no protein is detected.

Allele

Symbol: Psen1^tm1Shn
Name: targeted mutation 1, Jie Shen
MGI accession ID: MGI:1857974
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: PS1^-
Marker symbol: Psen1
Marker name: presenilin 1
Marker synonyms: ACNINV3; AD3; Ad3h; CMD1U; FAD; presenilin-1; PS1; PS-1; PSNL1; S182
Chromosome: 12
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
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.