B6N.129-Ptpn5^tm1Pjlo/J

Stock number: 016556
Research areas: Cell Biology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

In this STEP KO strain, a neo cassette replaces the catalytic site of the protein tyrosine phosphatase, non-receptor type 5 (Ptpn5) gene, abolishing gene expression. These mice may be useful for studying the role of STEP in regulating synaptic plasticity in Alzheimer's Disease.

Detailed description

In this STEP KO strain, a neo cassette replaces the catalytic site of the protein tyrosine phosphatase, non-receptor type 5 (Ptpn5) gene, abolishing gene expression. Homozygotes are viable, fertile, and normal in size. Striatal enriched protein phosphatase (STEP) is a neuron-specific tyrosine phosphatase which regulates synaptic plasticity following glutamatergic and dopaminergic input. Expressed mainly in the striatum, hippocampus, amygdala, and cortex of the brain, glutamate-activated STEP controls synaptic plasticity through limiting the duration of ERK 1/2 MAP kinase activity and by endocytosis of glutamate receptors. Activation of ERK1/2 in STEP-expressing regions of the brain is required for memory formation and learning. STEP levels are also shown to be increased in prefrontal cortex of Alzheimer's Disease (AD) models. Homozygous STEP KO mice lack expression of all STEP isoforms, and exhibit enhanced phosphorylation of ERK1/2 in the striatum, hippocampus, and amygdala, with slight elevation in the lateral septum. Heterozygous mice display a 50% reduction in STEP expression when compared to wildtype littermates. This decrease in STEP levels reverses cognitive and cellular deficits observed in AD mice, and blocks internalization of glutamate receptors. These mice may be useful for studying the role of STEP in regulating synaptic plasticity in Alzheimer's Disease.

Development

A targeting vector was designed to replace 1284 bp of genomic sequence, including the catalytic site, of the protein tyrosine phosphatase, non-receptor type 5 (Ptpn5) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric mice were bred to C57BL/6NCrl mice to generate a colony of STEP KO mice. These mice were backcrossed 10 generations to C57BL/6NCrl background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Ptpn5^tm1Pjlo
Name: targeted mutation 1, Paul J Lombroso
MGI accession ID: MGI:3835526
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: STEP^-
Marker symbol: Ptpn5
Marker name: protein tyrosine phosphatase, non-receptor type 5
Marker synonyms: PTPSTEP; STEP; STEP61
Chromosome: 7
Strain of origin: 129
Molecular note: 1284 bp of genomic sequence encoding the catalytic site was replaced with a neo cassette. The absence of protein expression was confirmed by western blot analysis on brain extracts.