Overview

This spontaneous 2 base pair deletion provides a viable recessive allele, which causes thyroid defects, neovascular retinaopathy, sperm defects, and hair cell loss in the crista ampullaris and organ of Corti, phenotypes that are distinct from those of a targeted disruption that causes homozygous embryonic lethal before implantation. This allele is valuable in characterizing this component of the AP-1 complex.

Genetic overview

Genetic Background	Generation
	N2F21 (2020-04-23 00:00:00)

Ap1g1^fgt

Allele Type	Gene Symbol	Gene Name
Spontaneous (Hypomorph)	Ap1g1	adaptor protein complex AP-1, gamma 1 subunit

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Research Applications

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Base Price

Starting at:

$215.26 Domestic price for female

430.51 Domestic price for breeder pair

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Details

Detailed Description

The recessive figure eight mutation causes thyroid defects, neovascular retinaopathy, sperm defects, and hair cell loss in the crista ampullaris and organ of Corti. Homozygotes display head tilting and circling behaviors and an inability to orient in water to swim. By one month of age ABR thresholds are elevated by approximately 40 dB across all frequencies, and by six months of age homozygotes have no detectable ABR, even at 100 dB. Histology of the inner ears at one month of age found no cochlear abnormalities, but by three months of age there is complete degeneration of the organ of Corti. Scanning electron microscopy of the organ of Corti at 5 weeks of age revealed the absence of some outer hair cell bundles, greatest near the apex and base, but normal inner hair cells and normal orientation and patterning of hair cells. Vestibular hair cell loss was also found in cross sections of the crista ampullaris. Scattered depigmented spots of the retina are found at 6 weeks of age, which develop into large depigmented areas by 16 weeks of age and newly formed vessels are found in the retina at both time points. Choroidal neovascularization with leakage was found by fluorescein angiography. Despite these defects, electroretinaograms showed normal amplitudes at 16 weeks of age. Homozygotes also have thyroid defects, with only a few normal follicles and many highly proliferating epithelial cells found at 15 weeks of age. Serum T4 levels are lower than normal, and homozygotes have a reduced body size, with females weighing an average of 5.9g less and males 3g less than controls between 4 and 6 weeks of age. Homozygous males have reduced fertility, but do reproduce. The germinal epithelium of the testes is disorganized, there are fewer maturing sperm cells, reduced total concentration of spermatozoa, and reduced sperm motility, with nearly half of the mature spermatozoa having their tail bent at the mid-piece. Nevertheless, all meiotic stages are present in the seminiferous tubules.

Development

The figure eight mutation arose spontaneously at The Jackson Laboratory in the strain C57BL/6-Tg(APOA1)1Rub/J and a mutant was bred to C57BL/6J and genotyped to select against Tg(APOA1)1Rub. One additional backcross to C57BL/6J was done before the strain was maintained by sibling breeding heterozygous females with, primarily, homozygous males.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Johnson KR; Gagnon LH; Chang B. 2016. A hypomorphic mutation of the gamma-1 adaptin gene (Ap1g1) causes inner ear, retina, thyroid, and testes abnormalities in mice. Mamm Genome 27(5-6):200-12PubMed: 27090238 MGI: J:230572

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Genetics

Ap1g1^fgt

Allele Symbol: Ap1g1^fgt

Allele Name	figure eight
Allele Type	Spontaneous (Hypomorph)
Allele Synonym(s)
Gene Symbol and Name	Ap1g1, adaptor protein complex AP-1, gamma 1 subunit
Gene Synonym(s)
Strain of Origin	C57BL/6-Tg(APOA1)1Rub/J
Chromosome	8
Molecular Note	This spontaneous 6 bp deletion of TTTCTG in exon 13 of NM009677, isoform 1, and exon 12 of Nm002301211, isoform 2, is predicted to cause an in-frame deletion of F391 and L392 of isoform 1, or F388 and L389 of isoform 2, amino acids which are in the adaptin N-terminal homology domain involved in interactions with other subunitos of the AP-1 complex.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

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

Genotype: Ap1g1^fgt/Ap1g1^fgt
C57BL/6-Ap1g1/KjnBoc

behavior/neurological phenotype

circling
- Background Sensitivity - although only approximately 70 of homozygotes on mixed C57BL/6J x C3HeB/FeJ background display head tossing and circling, it is higher on the pure C57BL/6J background

head tilt

head tossing
- Background Sensitivity - although only approximately 70 of homozygotes on mixed C57BL/6J x C3HeB/FeJ background display head tossing and circling, it is higher on the pure C57BL/6J background

impaired swimming

endocrine/exocrine gland phenotype

abnormal thyroid follicle morphology

abnormal thyroid follicular cell morphology

abnormal thyroid gland morphology
- at 16 weeks of age only a few normal follicles are found, there are highly proliferating epithelial cells that give rise to goiters, and the T4 levels are significantly lower than normal especially at younger ages

growth/size/body region phenotype

decreased body weight
- females and, to a lesser degree, males have a lower body weight as assessed between 4 and 6 weeks of age

hearing/vestibular/ear phenotype

cochlear outer hair cell degeneration
- inner and outer hair cells are normal at 1 month of age, but by 5 weeks of age some outer hair cells are missing stereocilia bundles and this is greater near the apex and base of the cochlea than the mid-region

decreased cochlear outer hair cell number

decreased vestibular hair cell number

increased or absent threshold for auditory brainstem response
- by 1 month of age ABR thresholds are approximately 40 dB higher at all frequencies, and by 6 months of age there is no detectable ABR even at 100 dB

organ of Corti degeneration
- at 1 month of age the cochlear structures are fairly normal, but by 3 months of age the organ of Corti is completely degenerated

vestibular hair cell degeneration
- cross-sectional analysis of the crista ampullaris shows loss of vestibular hair cells

homeostasis/metabolism phenotype

decreased circulating thyroxine level

nervous system phenotype

cochlear outer hair cell degeneration
- inner and outer hair cells are normal at 1 month of age, but by 5 weeks of age some outer hair cells are missing stereocilia bundles and this is greater near the apex and base of the cochlea than the mid-region

decreased cochlear outer hair cell number

decreased vestibular hair cell number

vestibular hair cell degeneration
- cross-sectional analysis of the crista ampullaris shows loss of vestibular hair cells

reproductive system phenotype

asthenozoospermia

decreased male germ cell number
- although all meiotic stages are present in the seminiferous tubules, the number of maturing sperm cells is reduced in homozygotes by approximately 40%

kinked sperm flagellum
- approximately 30 to 50% of mature spermatozoa have tails that are bent at the mid-piece

oligozoospermia

reduced male fertility

vision/eye phenotype

choroidal neovascularization
- fluorescein angiography shows choroidal neovacularization with leakage, and newly formed vessels are evident by histology at 6 and 16 weeks of age, although retonograms show normal amplitudes at 16 weeks of age

retinal degeneration
- in older homozygotes

retinal spots
- scattered depigmented spots are found by 6 weeks of age and large depigmented areas are found by 16 weeks of age

cardiovascular system phenotype

choroidal neovascularization
- fluorescein angiography shows choroidal neovacularization with leakage, and newly formed vessels are evident by histology at 6 and 16 weeks of age, although retonograms show normal amplitudes at 16 weeks of age

cellular phenotype

asthenozoospermia

decreased male germ cell number
- although all meiotic stages are present in the seminiferous tubules, the number of maturing sperm cells is reduced in homozygotes by approximately 40%

kinked sperm flagellum
- approximately 30 to 50% of mature spermatozoa have tails that are bent at the mid-piece

oligozoospermia

Genotype: Ap1g1^fgt/Ap1g1^fgt
involves: C3HeB/FeJ * C57BL/6J

behavior/neurological phenotype

circling
- Background Sensitivity - in the (C57BL/6J x C3HeB/FeJ) x C57BL/6J backcross mapping population the circling and head tossing phenotypes has only approximately 70% penetrance instead of the complete penetrance on the C57BL/6 background

head tossing

References

Johnson KR; Gagnon LH; Chang B. 2016. A hypomorphic mutation of the gamma-1 adaptin gene (Ap1g1) causes inner ear, retina, thyroid, and testes abnormalities in mice. Mamm Genome 27(5-6):200-12PubMed: 27090238 MGI: J:230572

Additional - Ap1g1^fgt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Ap1g1
- Genotyping resources and troubleshooting
Breeding Considerations

Although homozygous males have reduced fertility, they are generally adequate breeders to maintain a colony. Cryopreserved sperm from homozygous males has failed in in vitro fertilization efforts. Because the spinning of the homozygote can interfere with the rearing of the pups it is best to remove the homozygous male before birth and if homozygous females are used for breeding it is best to foster the pups.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Homozygote
Citation
When using the C57BL/6-Ap1g1^fgt/KjnBoc mouse strain in a publication, please cite the originating article(s) and include JAX stock #006487 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

MGL277 (Low)

Pricing & Availability

Availability Varies

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Ap1g1<fgt>

Related Products and Services

Frozen Mouse Embryo	C57BL/6-Ap1g1<fgt>/KjnBoc	$2595.00
Frozen Mouse Embryo	C57BL/6-Ap1g1<fgt>/KjnBoc	$2595.00
Frozen Mouse Embryo	C57BL/6-Ap1g1<fgt>/KjnBoc	$3373.50
Frozen Mouse Embryo	C57BL/6-Ap1g1<fgt>/KjnBoc	$3373.50

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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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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ap1g1fgt

Allele Symbol: Ap1g1fgt

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ap1g1fgt/Ap1g1fgtC57BL/6-Ap1g1/KjnBoc

behavior/neurological phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

homeostasis/metabolism phenotype

nervous system phenotype

reproductive system phenotype

vision/eye phenotype

cardiovascular system phenotype

cellular phenotype

Genotype: Ap1g1fgt/Ap1g1fgtinvolves: C3HeB/FeJ * C57BL/6J

behavior/neurological phenotype

References

Additional - Ap1g1fgt related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

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

Ap1g1^fgt

Allele Symbol: Ap1g1^fgt

Genotype: Ap1g1^fgt/Ap1g1^fgt
C57BL/6-Ap1g1/KjnBoc

Genotype: Ap1g1^fgt/Ap1g1^fgt
involves: C3HeB/FeJ * C57BL/6J

Additional - Ap1g1^fgt related