Overview

Amphiphysin (Amph) targeted mutation mice have defects in synaptic vesicle recycling that are unmasked by stimulation suggest impairments at multiple stages of the cycle. These defects correlate with increased mortality due to rare irreversible seizures. Due to such seizures, animals die mainly between two and five months of age without other noticeable health problems. Approximately 50% of homozygotes survive to 10 months of age. Homozygotes exhibit major learning deficits.

Donating Investigator

Pietro De Camilli, Yale University School of Medicine, HHMI

Genetic overview

Genetic Background	Generation

Amph^tm1Pdc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Amph	amphiphysin

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Research Applications

Developmental Biology Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In addition to ablated activity of the targeted gene, these mice show a parallel dramatic reduction in amphiphysin 2 selectivity in the brain due to its enhanced degradation in the absence of amphiphysin 1. Defects in synaptic vesicle recycling that are unmasked by stimulation suggest impairments at multiple stages of the cycle. These defects correlate with increased mortality due to rare irreversible seizures. Due to such seizures, animals die mainly between two and five months of age without other noticeable health problems. Approximately 50% of homozygotes survive to 10 months of age. Homozygotes exhibit major learning deficits as demonstrated by the Morris water maze task, and show very mild fear responses in both the context test and the auditory cue test compared to their wild-type littermates. Viable homozygotes reportedly breed until about three months of age and produce small litters of just two to three pups.

Development

A targeting vector was used to replace most of the 3' end of the first coding exon and a fragment of the following intron with PGK-neomycin resistance cassette placed in the same transcriptional orientation as the gene. The targeting vector was introduced to an 129SV/J agouti-derived embryonic stem (ES) cell line. Chimeras were bred to C57BL/6 by the donating laboratory (specific backcross generation unknown).

Selected References

Di Paolo G; Sankaranarayanan S; Wenk MR; Daniell L; Perucco E; Caldarone BJ; Flavell R; Picciotto MR; Ryan TA; Cremona O; De Camilli P. 2002. Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron 33(5):789-804PubMed: 11879655 MGI: J:75306

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Genetics

Amph^tm1Pdc

Allele Symbol: Amph^tm1Pdc

Allele Name	targeted mutation 1, Pietro De Camilli
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Amph, amphiphysin
Gene Synonym(s)
Strain of Origin	129/Sv
Chromosome	13
Molecular Note	Exon 1 was disrupted by the insertion of a neomycin selection cassette. Protein was undetected by Western blot analysis and immunofluorescence staining.
Mutations Made By	Pietro De Camilli, Yale University School of Medicine, HHMI

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Postnatal Lethality
  - Homozygous
Neurobiology Research
- Behavioral and Learning Defects
- Neurotransmitter Receptor and Synaptic Vesicle Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Amph^tm1Pdc/Amph^tm1Pdc
involves: 129/Sv * C57BL/6

behavior/neurological phenotype

abnormal contextual conditioning behavior
- at 5-7 months of age, homozygotes display longer escape latencies to locate a visible platform over the course of 4 days in the Morris water maze test

abnormal cued conditioning behavior
- in the fear conditioning task, 5- to 7-month-old homozygotes exhibit significantly less freezing behavior than wild-type mice in both the context test and the auditory cue test

abnormal spatial learning
- at 5-7 months of age, homozygotes display severe learning deficits in the Morris water maze hidden platform task
- in a transfer test in which the hidden platform is removed following training, mutants display a significantly lower number of crossings over the original platform location and spend significantly less time in the target quadrant than wild-type mice

increased susceptibility to pharmacologically induced seizures
- ic phase and tonic extension and death phase, respectively) than wild-type mice
- in response to repeated i.p. injections of metrazol (an epileptogenic GABA_A receptor antagonist), 12-week-old homozygotes show a normal initial response ("first twitch" phase) but progress significantly faster to the next two phases (tonic-clonic phase and tonic extension and death phase, respectively) than wild-type mice

tonic seizures
- homozygotes exhibit rare spontaneous seizures that reach a tonic extension and fail to resolve

mortality/aging

premature death
- homozygotes generally die between 2 and 5 months of age from rare irreversible seizures
- only 50% of homozygotes survive to 10 months of age

nervous system phenotype

abnormal synaptic vesicle recycling
- mutant nerve terminals
- after synapse stimulation, synapses of cultured cortical neurons obtained from mutant mice display defects in synaptic vesicle recycling, including a 25-30% smaller recycling vesicle pool size, slower destaining kinetics, and delayed vesicle repriming in mutant nerve terminals
- Normal - however, the ultrastructure of the synapse (including the total number of synaptic vesicles per synapse) is unaffected and no accumulation of endoyctic intermediates is observed, indicating that synaptic vesicle endocytosis is largely normal

increased susceptibility to pharmacologically induced seizures
- ic phase and tonic extension and death phase, respectively) than wild-type mice
- in response to repeated i.p. injections of metrazol (an epileptogenic GABA_A receptor antagonist), 12-week-old homozygotes show a normal initial response ("first twitch" phase) but progress significantly faster to the next two phases (tonic-clonic phase and tonic extension and death phase, respectively) than wild-type mice

tonic seizures
- homozygotes exhibit rare spontaneous seizures that reach a tonic extension and fail to resolve

reproductive system phenotype

abnormal Sertoli cell morphology
- the number of membrane invaginations of tubulobulbar complexes formed at the apical cytoplasm of mutant Sertoli cells is ~50% of that in wild-type Sertoli cells

abnormal spermatid morphology
- mutant spermatids are absent at stage IX and X

abnormal spermiation
- at stage VIII, the number of unreleased spermatids in mutant testes is ~2-fold higher than that in wild-type testes, indicating that spermatid release and the following transition from stage VIII to IX is prolonged

abnormal spermiogenesis
- in mutant males, the ratio of stage VIII (defined as the stage with the latest spermatids) and stage IX (the stage immediately after spermatid release) is significantly higher and lower than that in wild-type mice, respectively
- Normal - no significant differences are observed in other spermatogenic stages

cellular phenotype

abnormal spermatid morphology
- mutant spermatids are absent at stage IX and X

endocrine/exocrine gland phenotype

abnormal Sertoli cell morphology
- the number of membrane invaginations of tubulobulbar complexes formed at the apical cytoplasm of mutant Sertoli cells is ~50% of that in wild-type Sertoli cells

References

Di Paolo G; Sankaranarayanan S; Wenk MR; Daniell L; Perucco E; Caldarone BJ; Flavell R; Picciotto MR; Ryan TA; Cremona O; De Camilli P. 2002. Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron 33(5):789-804PubMed: 11879655 MGI: J:75306

Additional - Amph^tm1Pdc related

Technical Support

CONTACT TECHNICAL SUPPORT

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

When maintained as a live colony, homozyogotes or heterozygotes may be bred. Homozygotes sometimes have seizures and may die at ~3 months of age. Surviving homozygotes do not breed well after they are 3 months of age. Homozygote x homozygote crosses produce small litters of 2-3 pups each.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129-Amph^tm1Pdc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008514 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
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Amph<tm1Pdc>

Related Products and Services

Frozen Mouse Embryo	B6;129-Amph<tm1Pdc>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129-Amph<tm1Pdc>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129-Amph<tm1Pdc>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6;129-Amph<tm1Pdc>/J Frozen Embryo	$3373.50

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Amphtm1Pdc

Allele Symbol: Amphtm1Pdc

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Amphtm1Pdc/Amphtm1Pdcinvolves: 129/Sv * C57BL/6

behavior/neurological phenotype

mortality/aging

nervous system phenotype

reproductive system phenotype

cellular phenotype

endocrine/exocrine gland phenotype

References

Additional - Amphtm1Pdc 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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Amph^tm1Pdc

Allele Symbol: Amph^tm1Pdc

Genotype: Amph^tm1Pdc/Amph^tm1Pdc
involves: 129/Sv * C57BL/6

Additional - Amph^tm1Pdc related