B6.D1-Pde10a^tm1Pfi/J

Stock number: 008210
Strain synonyms: PDE10A^C57
Research areas: Cell Biology Research, Neurobiology Research, Research Tools

Description

These PDE10A^C57 mutant mice are deficient in phosphodiesterase 10A activity, and may be useful in neurobiological studies including metabolic inactivation of intracellular signal transduction pathways by cyclic phosphodiesterases (PDEs), regulation of information processing by basal ganglia circuitry, and striatal hypofunction or psychotic disease.

Detailed description

Mice homozygous for the phosphodiesterase 10A (PDE10A) targeted mutation are viable and fertile with no gross abnormalities, although breeding homozygotes together produces reduced liter sizes. The targeted gene generates a truncated transcript. A small amount of functionally inactive protein is detected in striatum, cortex and cerebellum. Homozygous mice on the C57BL/6N genetic background (PDE10A^C57) exhibit multiple behavioral abnormalities; decreased locomotor activity when placed in a novel environment, delayed acquisition of conditioned avoidance response, blunted response to the NMDA receptor antagonist MK-801 (but not PCP), altered locomotor responses to both amphetamine and methamphetamine, and increased striatal dopamine utilization. These PDE10A^C57 mutant mice may be useful in neurobiological studies including metabolic inactivation of intracellular signal transduction pathways by cyclic phosphodiesterases (PDEs), regulation of information processing by basal ganglia circuitry, and striatal hypofunction or psychotic disease.

Development

A targeting vector was designed to replace exons 14-16 of the targeted gene (coding for basepairs 1499-1861 of the mRNA) with a PGK-neo cassette. The construct was electroporated into DBA/1LacJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric males were bred with DBA/1LacJ females to produce heterozygous mutant mice. After, mutant mice were backcrossed to C57BL/6N for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6NJ inbred mice (Stock No. 005304) to establish the colony.

Allele

Symbol: Pde10a^tm1Pfi
Name: targeted mutation 1, Pfizer, Ltd
MGI accession ID: MGI:3663426
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Pde10a
Marker name: phosphodiesterase 10A
Chromosome: 17
Strain of origin: DBA/1LacJ
Molecular note: A PGK-neo vector was designed to replace exons 14-16, corresponding to bases 1499-1861 of the coding region. Sequence analysis revealed that the neo cassette was spliced out. The resulting transcript encoded an in-frame deletion of 126 amino acids at the N-terminus of the catalytic domain. This terminus contained one of the two divalent zinc binding sites. Since the deletion was in-frame, a mutant protein of approximately 75 kDa could be produced.