129-Synpo^tm1Mndl/J

Stock number: 028822
Product name: Synpo^-
Research areas: Developmental Biology Research, Neurobiology Research

Description

Synpo^-/- mice have a β-gal gene replacing the coding region of the synaptopodin gene. These mice may be useful for studying plasticity of spine apparatuses in the brain and plasticity of the podocyte actin cytoskeleton.

Detailed description

Synpo^-/- mice have a β-galactosidase gene and a loxP-flanked neomycin resistance (neo) cassette replacing the coding region of the synaptopodin (Synpo) gene, abolishing gene expression. Homozygous mice are viable and fertile. Synaptopodin is an actin-associated protein involved in the formation and maintenance of spine apparatuses in the spines of excitatory neurons in the olfactory bulb, cerebral cortex, striatum, and hippocampus. Synaptopodin is essential for the regulation of dendritic spine dynamics and synaptic plasticity. Although the number and length of dendritic spines on cortical neurons are normal in Synpo^-/- mice, the neurons lack spine apparatuses. These mice exhibit a reduction in hippocampal long-term potentiation (LTP) in the hippocampus and impairment of spatial learning. Synpo is also expressed in renal podocytes, where it is part of the actin-based contractile apparatus in the foot processes. Synpo^-/- podocytes have delayed actin filament reformation after protamine sulfate-induced podocyte foot process effacement. These podocytes show an upregulation of Synpo-T isoform expression.

Development

A targeting vector was designed to replace the coding region of the synaptopodin (Synpo) gene with a β-galactosidase gene and a loxP-flanked neomycin resistance (neo) cassette inserted downstream of the ATG start site. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to 129 females. Resulting offspring were bred to 129 mice for at least 10 generations to generate a colony of Synpo^-/-. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize 129S1/SvImJ oocytes (Stock No. 002448).

Allele

Symbol: Synpo^tm1Mndl
Name: targeted mutation 1, Peter Mundel
MGI accession ID: MGI:2675703
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Synpo
Marker name: synaptopodin
Chromosome: 18
Strain of origin: 129P2/OlaHsd
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: Olfactory bulb neurons, cerebral cortex, striatum, and hippocampus.
Molecular note: The coding region has been replaced by a lacZ gene fused in frame just downstream of the ATG start codon. A neomycin resistance gene flanked by loxP sites was then inserted downstream of lacZ. Lack of the protein product was then confirmed by Western blot analysis and by immunostaining.