Overview

Mice that are homozygous for the Pick1 (protein interacting with C kinase 1) targeted mutation exhibit several deficits in synaptic plasticity in different brain regions.

Donating Investigator

Richard L Huganir, Johns Hopkins University School of Medicine

Genetic overview

Genetic Background	Generation

Pick1^tm1Rlh

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Pick1	protein interacting with C kinase 1

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous males are not fertile, however. No gene product (protein) is detected by Western blot analysis of the brain isolated from homozygous animals. Mutant mice exhibit several deficits in synaptic plasticity in different brain regions. These mice may be useful in studies of the trafficking and localization of GluR2-containing receptors and calcium-permeable AMPA receptor plasticity (CARP).

Development

LoxP sites flanking both exon3 and a neomycin cassette were introduced using (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to CMV-cre transgenic mice to delete exon 3 and the neomycin cassette. The CMV-Cre transgene was bred out from the line. This strain was backcrossed to C57BL/6J for at least 11 generations by the donating laboratory.

Selected References

Gardner SM; Takamiya K; Xia J; Suh JG; Johnson R; Yu S; Huganir RL. 2005. Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron 45(6):903-15PubMed: 15797551 MGI: J:99813

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Genetics

Pick1^tm1Rlh

Allele Symbol: Pick1^tm1Rlh

Allele Name	targeted mutation 1, Richard L Huganir
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	PICK1^-; PICK1-KO
Gene Symbol and Name	Pick1, protein interacting with C kinase 1
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	15
General Note	Phenotypic Similarity to Human Syndrome: Globozoospermia in homozygous mice (J:149846)
Molecular Note	Exon 3 was deleted via cre-mediated recombination, resulting in a frame-shift mutation. Western blot of mutant brains confirmed absence of protein.
Mutations Made By	Richard Huganir, Johns Hopkins University School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Receptor Defects
  - glutamate receptor: ionotropic

Mammalian Phenotype Terms by Genotype

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

Genotype: Pick1^tm1Rlh/Pick1^tm1Rlh
involves: 129S1/Sv * 129X1/SvJ

endocrine/exocrine gland phenotype

small testis
- homozygous mutant testes are smaller than those of wild-type and heterozygous mice

decreased testis weight
- normalized testis weights of homozygous mutant mice are significantly lower than those of both wild-type and heterozygous mice

small seminiferous tubules
- the diameter of homozygous mutant seminiferous tubules is significantly smaller than that of wild-type and heterozygous tubules

nervous system phenotype

absent long term depression
- cerebellar LTD is absent in Pick1-deficient mice as measured in dissociated cerebellar cultures and in parasagittal brain slices from P20-25 mice; transfection of cultured neurons with full length wild-type Pick1 cDNA rescues LTD

reproductive system phenotype

globozoospermia
- ~90% of mutant sperm lack the typical hook-shaped head of wild-type sperm; instead, they have round or irregular ball-like heads
- globozoospermia is likely a consequence of abnormal trafficking of proacrosomal granules resulting in impaired formation of acrosomes

small testis
- homozygous mutant testes are smaller than those of wild-type and heterozygous mice

oligozoospermia
- up>6 ¿ 1.10 ¿ 10⁶)
- the total number of sperm from the cauda epididymis of adult homozygotes (7.24 ¿ 10⁶ ¿ 0.81 ¿ 10⁶) is significantly lower than that of wild-type (17.69 ¿ 10⁶ ¿ 1.62 ¿ 10⁶) and heterozygous controls (12.41 ¿ 10⁶ ¿ 1.10 ¿ 10⁶)

abnormal sperm flagellum morphology
- mutant mitochondrial sheaths exhibit various defects, including abnormal sperm with aggregated mitochondrial sheaths, split mitochondrial sheaths, mitochondrial sheaths overlapping with the round nucleus, and in some cases wrapping around the round nucleus
- s

abnormal spermiogenesis
- sperm abnormalities are likely occur in the transition from round spermatids to mature sperm during spermiogenesis

abnormal acrosome morphology
- fragmentation of acrosomes occurs in the early stages of spermiogenesis
- mutant acrosomes fail to acquire the crescent moon-shaped structure, are frequently fragmented, and abnormally positioned
- fragmented

asthenozoospermia
- the number of motile mutant sperm is less than 4% of that from wild-type littermates
- none of the mutant sperm display rapid progressive linear motility

small seminiferous tubules
- the diameter of homozygous mutant seminiferous tubules is significantly smaller than that of wild-type and heterozygous tubules

decreased testis weight
- normalized testis weights of homozygous mutant mice are significantly lower than those of both wild-type and heterozygous mice

abnormal sperm nucleus morphology
- elongation of the nuclei of mutant spermatids is impaired in the late stages of spermiogenesis resulting in round-shaped nuclei
- ~90% of mutant sperm from the cauda epididymis are round-headed with deformed (round) nuclei
- impaired nucleus formation

male infertility
- male homozygotes copulate normally but are completely infertile

teratozoospermia
- ~90% of mutant sperm from the cauda epididymis are round-headed with abnormal acrosomes, abnormal nuclear shapes, and abnormal mitochondrial sheaths

abnormal male germ cell apoptosis
- TUNEL staining indicates significantly more apoptotic germ cells, many of them spermatids, in mutant seminiferous tubules than in wild-type tubules (2.5% vs 0.4%, respectively), suggesting increased apoptosis during late stages of spermatogenesis

cellular phenotype

abnormal sperm flagellum morphology
- mutant mitochondrial sheaths exhibit various defects, including abnormal sperm with aggregated mitochondrial sheaths, split mitochondrial sheaths, mitochondrial sheaths overlapping with the round nucleus, and in some cases wrapping around the round nucleus
- s

abnormal sperm nucleus morphology
- elongation of the nuclei of mutant spermatids is impaired in the late stages of spermiogenesis resulting in round-shaped nuclei
- ~90% of mutant sperm from the cauda epididymis are round-headed with deformed (round) nuclei
- impaired nucleus formation

abnormal male germ cell apoptosis
- TUNEL staining indicates significantly more apoptotic germ cells, many of them spermatids, in mutant seminiferous tubules than in wild-type tubules (2.5% vs 0.4%, respectively), suggesting increased apoptosis during late stages of spermatogenesis

globozoospermia
- ~90% of mutant sperm lack the typical hook-shaped head of wild-type sperm; instead, they have round or irregular ball-like heads
- globozoospermia is likely a consequence of abnormal trafficking of proacrosomal granules resulting in impaired formation of acrosomes

teratozoospermia
- ~90% of mutant sperm from the cauda epididymis are round-headed with abnormal acrosomes, abnormal nuclear shapes, and abnormal mitochondrial sheaths

abnormal acrosome morphology
- fragmented
- mutant acrosomes fail to acquire the crescent moon-shaped structure, are frequently fragmented, and abnormally positioned
- fragmentation of acrosomes occurs in the early stages of spermiogenesis

asthenozoospermia
- none of the mutant sperm display rapid progressive linear motility
- the number of motile mutant sperm is less than 4% of that from wild-type littermates

oligozoospermia
- the total number of sperm from the cauda epididymis of adult homozygotes (7.24 ¿ 10⁶ ¿ 0.81 ¿ 10⁶) is significantly lower than that of wild-type (17.69 ¿ 10⁶ ¿ 1.62 ¿ 10⁶) and heterozygous controls (12.41 ¿ 10⁶ ¿ 1.10 ¿ 10⁶)
- up>6 ¿ 1.10 ¿ 10⁶)

The following phenotype relates to a compound genotype created using this strain

Genotype: Pick1^tm1Rlh/Pick1^tm1Rlh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system phenotype

impaired synaptic plasticity
- following high-frequency stimulation on the cerebellum slice culture, no increase in the rectification ratio was observed, indicating that calcium-permeable AMPA receptor plasticity (CARP) does not occur in these mutant mice

References

Gardner SM; Takamiya K; Xia J; Suh JG; Johnson R; Yu S; Huganir RL. 2005. Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron 45(6):903-15PubMed: 15797551 MGI: J:99813

Additional - Pick1^tm1Rlh related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Pick1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintained as a live colony, heterozygotes may be bred. Homozygous females are infertile.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129-Pick1^tm1Rlh/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008891 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

Cryo Recovery

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-Type for Pick1<tm1Rlh>

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Frozen Mouse Embryo	B6.129-Pick1<tm1Rlh>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Pick1<tm1Rlh>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Pick1<tm1Rlh>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129-Pick1<tm1Rlh>/J Frozen Embryo	$3373.50

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The Jackson Laboratory's Genotype Promise

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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Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Pick1tm1Rlh

Allele Symbol: Pick1tm1Rlh

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Pick1tm1Rlh/Pick1tm1Rlhinvolves: 129S1/Sv * 129X1/SvJ

endocrine/exocrine gland phenotype

nervous system phenotype

reproductive system phenotype

cellular phenotype

Genotype: Pick1tm1Rlh/Pick1tm1Rlhinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system phenotype

References

Additional - Pick1tm1Rlh 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Pick1^tm1Rlh

Allele Symbol: Pick1^tm1Rlh

Genotype: Pick1^tm1Rlh/Pick1^tm1Rlh
involves: 129S1/Sv * 129X1/SvJ

Genotype: Pick1^tm1Rlh/Pick1^tm1Rlh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Pick1^tm1Rlh related