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| These PDE10AC57 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. | |||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names B6.D1-Pde10atm1Jasi/J (Changed: 28-AUG-08 ) Type Congenic; Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Frank Menniti, Pfizer Inc 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 (PDE10AC57) 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 PDE10AC57 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.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| 005304 C57BL/6NJ | ||
| Considerations for Choosing Controls | ||
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Pde10atm1Pfi/Pde10atm1Pfi
DBA/1LacJ-Pde10atm1Pfi
- growth/size phenotype
- decreased body weight (MGI Ref ID J:111662)
- female homozygotes have significantly lower body weights than corresponding wild-type mice (12% decrease) while body weight in males is equivalent in mutants and wild-type
- behavior/neurological phenotype
- decreased exploration in new environment (MGI Ref ID J:111662)
- mutants show decreased exploratory and/or locomotor activity in open field tests
- hypoactivity (MGI Ref ID J:111662)
- male homozygotes show decreased locomotor activity compared to wild-type males when placed in a novel environment (29% decrease in locomotor activity at 30 minutes); difference disappears by 60 minutes
- in an elevated plus maze test, no differences in open arm entries or time spent in open arms are observed, but the total distance traveled by homozygotes is significantly less than wild-type (28% decrease in males, 17% decrease in females)
- homeostasis/metabolism phenotype
- abnormal enzyme/coenzyme activity (MGI Ref ID J:111662)
- phospodiesterase (PDE) activity immunoprecipitated from the striatum is substantially reduced in homozygotes vs wild-type; null mice lack PDE activity while heterozygotes have only slightly less activity than wild-type
- no difference in activity precipitated from the cortex is seen between homozygotes, heterozygotes and wild-type
This mouse can be used to support research in many areas including:
Cell Biology Research
Signal Transduction
Neurobiology Research
Behavioral and Learning Defects
Cerebellar Defects
Cortical Defects
Research Tools
Neurobiology Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Pde10atm1Pfi | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Pfizer, Ltd | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Pde10-; Pde10atm1Jasi; | ||
| Mutation Made By | Judith Siuciak, Pfizer Inc | ||
| Strain of Origin | DBA/1LacJ | ||
| Gene Symbol and Name | Pde10a, phosphodiesterase 10A | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | FLJ11894; FLJ25677; HSPDE10A; Pde10a3; | ||
| 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 theN-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. [MGI Ref ID J:111662] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Pde10atm1Jasi, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Siuciak JA; McCarthy SA; Chapin DS; Fujiwara RA; James LC; Williams RD; Stock JL; McNeish JD; Strick CA; Menniti FS; Schmidt CJ. 2006. Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: evidence for altered striatal function. Neuropharmacology 51(2):374-85. [PubMed: 16769090] [MGI Ref ID J:111662]
Siuciak JA; McCarthy SA; Chapin DS; Martin AN; Harms JF; Schmidt CJ. 2008. Behavioral characterization of mice deficient in the phosphodiesterase-10A (PDE10A) enzyme on a C57/Bl6N congenic background. Neuropharmacology 54(2):417-27. [PubMed: 18061215] [MGI Ref ID J:133637]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred together, or with C57BL/6NJ inbred mice (see Stock No. 005304). As reduced pup production is observed, the donating investigator does not recommend maintaining the colony by breeding homozygous mice together.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date:
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| 005304 C57BL/6NJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
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