B6.129-Serpini1^tm1Dpw/J

Stock number: 019121
Product name: Ns-
Research areas: Neurobiology Research

Description

Exon 2 of the Serpini1 gene is disrupted in this knockout strain. Homozygotes exhibit anxiety-like, neophobic behavior and have applications in studies of Familial Encephalopathy with Neuroserpin Inclusion Bodies, synaptic plasticity, learning and memory.

Detailed description

Neuroserpin, in the serpin family of serine protease inhibitors, targets tissue plasminogen activator. Neuroserpin has a neuroprotective effect in the brain during hypoxia/ischemia. The neurodegenerative disease, Familial Encephalopathy with Neuroserpin Inclusion Bodies, is caused by mutations in neuroserpin that result in formation and accumulation of intracellular polymers. Mice that are homozygous for this targeted mutation of the Serpini1 (serine (or cysteine) peptidase inhibitor, clade I, member 1) gene are viable and fertile. No gene product (protein) is detected by Western blot analysis of brain protein extracts from homozygotes. Immunofluorescent labeling of hippocampal sections from homozygous mice does not detect the protein. Homozygotes on the mixed B6;129 background exhibit anxiety-like (hypoactivity) behavior to novelty and reduced exploration behavior. Heterozygotes on the mixed B6;129 background exhibit an intermediate behavioral phenotype.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

Dr. Peter Sonderegger, while at University of Zurich, Zurich, Switzerland, designed a targeting vector that contained a PGK-NEO cassette (in opposite orientation) and was used to disrupt exon 2, which includes the ATG translation start codon. The construct was electroporated into 129/Sv derived GS1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 10 generations by Dr. Daniel Lawrence, while at University of Michigan. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Serpini1^tm1Dpw
Name: targeted mutation 1, David Paul Wolfer
MGI accession ID: MGI:2668495
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Serpini1
Marker name: serine (or cysteine) peptidase inhibitor, clade I, member 1
Chromosome: 3
Strain of origin: 129/Sv
Molecular note: A neo cassette was inserted into exon 2. Western blot analysis demonstrated the absence of gene product in homozygotes.