B6.129-Dlg4^tm1Rlh/J

Stock number: 013099
Product name: PSD95 null
Research areas: Neurobiology Research

Description

Homozygous Dlg4 (discs, large homolog 4 (Drosophila); PSD95) targeted mutation mice completely lack protein expression in the brain. By approximately the second week of life, a reduction in the synaptic expression of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs), but not N-methyl-D-aspartate receptors (NMDARs) is apparent. This strain may be useful for further characterizing the role of this gene in glutamatergic neurotransmission.

Detailed description

Homozygous Dlg4 (discs, large homolog 4 (Drosophila); PSD95) targeted mutation mice completely lack protein expression in the brain. No gross anatomical or obvious behavioral abnormalities are apparent in these mice. By approximately the second week of life, a reduction in the synaptic expression of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs), but not N-methyl-D-aspartate receptors (NMDARs) is apparent. AMPAR function is impaired due to an increase in the proportion of synapses that lack functional AMPARs (silent synapses) rather than a general decline in activity. Frequency, but not amplitude, of AMPAR-mediated miniature excitatory postsynaptic currents (EPSCs) is reduced. Decay kinetics of NMDAR-mediated synaptic currents are slower and the magnitude of long-term potentiation (LTP) is greater in homozygotes. This strain may be useful for further characterizing the role of this gene in glutamatergic neurotransmission.

Development

A neomycin resistance cassette replaces a genomic region including six exons that encode the PDZ1 and PDZ2 domains of the targeted gene. The mutation was created in (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. This strain was crossed to C57BL/6 for ten generations by the donating laboratory.

Allele

Symbol: Dlg4^tm1Rlh
Name: targeted mutation 1, Richard L Huganir
MGI accession ID: MGI:3700207
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Dlg4
Marker name: discs large MAGUK scaffold protein 4
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Exons encoding PDZ 1 and 2 domains were replaced with a neomycin resistance cassette. This results in the production of an out of frame transcript. Western blot confirmed absence of protein in mutant mice.