Overview

Also Known As:Nte-

These Pnpla6 knock-out mice exhibit an embryonic lethal phenotype, and neuropathy target esterase activity in brain tissue is reduced.

Donating Investigator

Carrolee Barlow, Brain Cells Inc

Genetic overview

Genetic Background	Generation

Pnpla6^tm1Blw

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Pnpla6	patatin-like phospholipase domain containing 6

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Research Applications

Research Tools
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Homozygous null mice have an embryonic lethal phenotype, failing to develop past embryonic day 8.5. Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and are more active than wildtype littermates. A reduced level of protein gene product is detected by immunoprecipitation and Western blot analysis of brain, testes and kidney, but protein levels are not reduced in liver. Beta galactosidase activity in heterozygotes aged embryonic day 13.5 is found in the developing lens and spinal cord. In adult heterozygotes, beta galactosidase activity is detected throughout the brain, especially in the cerebellar Purkinje cells and hippocampus. Beta galactosidase activity patterns mimic the endogenous gene expression pattern. NTE activity in brain tissue is reduced by 40%. Heterozygotes are more sensitive to organophosphate toxicity with increased motor activity and mortality. This mutant mouse strain may be useful in studies of neuropathological hyperactivity, Gulf War Syndrome, and organophosphate-induced sub-acute neurotoxicity.

Development

A targeting vector containing lacZ, neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 4 to 10. The lacZ coding sequence was inserted into exon 4, and exons 5 to 10 were deleted. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals from two independent ES cell clones were crossed. The offspring were mated to 129S1/SvImJ (STOCK#2448) mice.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	lacZ expression in heterozygotes at embryonic day 13.5 is found in the developing lens and spinal chord. In adults, beta-galgalactosidase is detected throughout the brain, especially in the cerebellar Purkinje cells and the hippocampus.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Winrow CJ; Hemming ML; Allen DM; Quistad GB; Casida JE; Barlow C. 2003. Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity. Nat Genet 33(4):477-85PubMed: 12640454 MGI: J:82791

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Genetics

Pnpla6^tm1Blw

Allele Symbol: Pnpla6^tm1Blw

Allele Name	targeted mutation 1, Carrolee Barlow
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Nte^-
Gene Symbol and Name	Pnpla6, patatin-like phospholipase domain containing 6
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	lacZ expression in heterozygotes at embryonic day 13.5 is found in the developing lens and spinal chord. In adults, beta-galgalactosidase is detected throughout the brain, especially in the cerebellar Purkinje cells and the hippocampus.
Strain of Origin	129S6/SvEvTac
Chromosome	8
Molecular Note	The gene was disrupted by an in-frame fusion of lacZ to exon 4 and replacement of exons 5-10 with a neomycin resistance gene.
Mutations Made By	Christopher Winrow, Salk Institute for Biological Studies

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- Toxicology Research
- lacZ Expression
Neurobiology Research
- Behavioral and Learning Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Pnpla6^tm1Blw/Pnpla6^tm1Blw
involves: 129S6/SvEvTac * C57BL/6J

embryo phenotype

abnormal neural tube closure
- mutant embryos display abnormal closing of the neural tube

decreased embryo size
- at E9, mutant embryos appear runted

embryonic growth arrest
- mutant embryos are growth arrested at E10 and E11

embryonic growth retardation
- at E9, mutant embryos appear developmentally retarded relative to wild-type embryos

growth/size/body region phenotype

decreased embryo size
- at E9, mutant embryos appear runted

embryonic growth retardation
- at E9, mutant embryos appear developmentally retarded relative to wild-type embryos

mortality/aging

embryonic lethality during organogenesis, complete penetrance
- homozygotes are observed at a reduced frequency after E8; first signs of resorption are evident at E9
- no homozygotes are observed after E11

nervous system phenotype

abnormal neural tube closure
- mutant embryos display abnormal closing of the neural tube

Genotype: Pnpla6^tm1Blw/Pnpla6⁺
involves: 129S6/SvEvTac * C57BL/6J

behavior/neurological phenotype

hyperactivity
- after exposure to EOPF (1 mg per kg body weight), motor activity is significantly higher in wild-type mice than in heterozygous mutant mice, indicating that even a minor chemical reduction of enzyme activity can lead to hyperactivity
- heterozygotes display higher baseline levels of motor activity than wild-type mice, as determined by total distance traveled and vertical rearing events in an open-field chamber over a 10-day test period

increased vertical activity
- after exposure to EOPF (1 mg per kg body weight), the number of vertical events is significantly higher in wild-type mice than in heterozygous mutant mice
- under baseline conditions, heterozygotes show a significantly higher number of vertical rearing events than wild-type mice over a 10-day test period in an open-field chamber

homeostasis/metabolism phenotype

increased sensitivity to xenobiotic induced morbidity/mortality
- heterozygotes exhibit significantly higher mortality rates than wild-type mice after i.p. injection of ethyl octylphosphonofluoridate (EOPF), an organophosphate compound that causes delayed neurotoxicity, at both 6 mg and 10 mg EOPF per kg body weight
- Normal - however, no mortality or neuropathological effects are noted in either wild-type or heterozygous mutant mice with 1 mg EOPF per kg body weight

mammalian phenotype

behavior/neurological phenotype
- Normal - under baseline conditions, heterozygotes display no gross defects in learning and memory or anxiety relative to wild-type mice

mortality/aging

increased sensitivity to xenobiotic induced morbidity/mortality
- heterozygotes exhibit significantly higher mortality rates than wild-type mice after i.p. injection of ethyl octylphosphonofluoridate (EOPF), an organophosphate compound that causes delayed neurotoxicity, at both 6 mg and 10 mg EOPF per kg body weight
- Normal - however, no mortality or neuropathological effects are noted in either wild-type or heterozygous mutant mice with 1 mg EOPF per kg body weight

References

Winrow CJ; Hemming ML; Allen DM; Quistad GB; Casida JE; Barlow C. 2003. Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity. Nat Genet 33(4):477-85PubMed: 12640454 MGI: J:82791

Additional - Pnpla6^tm1Blw related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Pnpla6
- Genotyping resources and troubleshooting
Breeding Considerations

This strain is maintained as a heterozygote due to homozygous embryonic lethality. Heterozygotes are more active than wildtype littermates.
- Additional Breeding and Husbandry Support
Citation
When using the Nte- mouse strain in a publication, please cite the originating article(s) and include JAX stock #005091 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

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Not-For-Profit & Academic

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Pnpla6<tm1Blw>

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Also Known As:Nte-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Pnpla6tm1Blw

Allele Symbol: Pnpla6tm1Blw

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Pnpla6tm1Blw/Pnpla6tm1Blwinvolves: 129S6/SvEvTac * C57BL/6J

embryo phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

Genotype: Pnpla6tm1Blw/Pnpla6+involves: 129S6/SvEvTac * C57BL/6J

behavior/neurological phenotype

homeostasis/metabolism phenotype

mammalian phenotype

mortality/aging

References

Additional - Pnpla6tm1Blw related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Pnpla6^tm1Blw

Allele Symbol: Pnpla6^tm1Blw

Genotype: Pnpla6^tm1Blw/Pnpla6^tm1Blw
involves: 129S6/SvEvTac * C57BL/6J

Genotype: Pnpla6^tm1Blw/Pnpla6⁺
involves: 129S6/SvEvTac * C57BL/6J

Additional - Pnpla6^tm1Blw related