Overview

These Gak^flox mutant mice possess loxP sites flanking exon 1 of the cyclin G associated kinase (Gak) gene. GAK functions as a cochaperone with Hspa8 (Hsc70). GAK is involved in the process of clathrin-mediated endocytosis and is critical to development.

Donating Investigator

Lois Greene, NIH

Genetic overview

Genetic Background	Generation

Gak^tm2Legr

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Gak	cyclin G associated kinase

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Research Applications

Research Tools

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Details

Detailed Description

These Gak^flox mutant mice possess loxP sites flanking exon 1 of the cyclin G associated kinase (Gak) gene. GAK, a cyclin-dependent protein kinase, is a multidomain protein that functions as a cochaperone with Hspa8 (Hsc70). GAK is involved in the process of clathrin-mediated endocytosis and is critical to development.
Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have a null allele in the cre-expressing tissues.

For example, when bred to mice carrying Tg(Nes-Cre)1Kln, neuronal Cre recombinase expression results in early lethality and a failure of neuroprogenitor cells to proliferate.

When bred to mice carrying Tg(Alb-cre)21Mgn, Cre recombinase expression in the liver results in lethality by day 5, jaundice, disorganized bile ducts, undifferentiated hepatoblasts, fragmented Golgi and failure to accumulate glycogen.

When bred to adult mice carrying Tg(CAG-cre/Esr1*)5Amc, tamoxifen-inducible cre-recombinase expression results in death within days of tamoxifen treatment.

When bred to mice carrying Tg(KRT14-Cre)1Amc, Cre recombinase expression results in the epidermis, results in postnatal lethality, a defective epidermal barrier and failure to differentiate epidermal layers.

Development

The targeting vector contains a loxP site followed by exon 1 and loxP-flanked PGK neomycin cassette. The construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice once and then maintained by sibling mating.

Control Suggestions

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Lee DW; Zhao X; Yim YI; Eisenberg E; Greene LE. 2008. Essential role of cyclin-G-associated kinase (Auxilin-2) in developing and mature mice. Mol Biol Cell 19(7):2766-76PubMed: 18434600 MGI: J:180119

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Genetics

Gak^tm2Legr

Allele Symbol: Gak^tm2Legr

Allele Name	targeted mutation 2, Lois E Greene
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	GAK^fl
Gene Symbol and Name	Gak, cyclin G associated kinase
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	5
Molecular Note	A loxP site was inserted upstream of exon 1. A floxed neo cassette was inserted downstream of exon 1.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Developmental Biology Research
  - Cre-lox System

Mammalian Phenotype Terms by Genotype

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

Genotype: Gak^tm2Legr/Gak^tm2Legr Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
involves: 129S6/SvEvTac * C57BL/6 * DBA

endocrine/exocrine gland phenotype

abnormal bile duct morphology
- not well organized

mortality/aging

postnatal lethality, complete penetrance
- by P5

growth/size/body region phenotype

increased body weight
- small during the first 4 days after birth

decreased body size
- at P1 or P2

homeostasis/metabolism phenotype

decreased liver glycogen level
- mice fail to accumulate glycogen unlike control mice

liver/biliary system phenotype

abnormal hepatoblast differentiation
- hepatoblasts fail to differentiate

abnormal liver morphology
- yellowish liver

decreased liver glycogen level
- mice fail to accumulate glycogen unlike control mice

abnormal bile duct morphology
- not well organized

jaundice
- at P1 or P2

Genotype: Gak^tm2Legr/Gak^tm2Legr Tg(Nes-cre)1Kln/0
involves: 129S6/SvEvTac * C57BL/6 * SJL

behavior/neurological phenotype

lethargy
- some mice are sluggish at P3

cellular phenotype

abnormal neuronal precursor proliferation
- reduced

abnormal neuron differentiation
- mice exhibit decreased numbers of neuronal precursors due to reduced proliferation and migration compared with control mice

mortality/aging

postnatal lethality, complete penetrance
- mice die between P3 and P21

nervous system phenotype

abnormal Ammon gyrus morphology
- decreased cell density

abnormal cortical ventricular zone morphology
- at P1, mice exhibit reduced cellularity and thickness of the cerebral cortex compared with control mice
- at E15.5, cellular density in the forebrain and hindbrain cortex is reduced compared to in control mice

abnormal dentate gyrus morphology
- decreased cell density

abnormal neuron differentiation
- mice exhibit decreased numbers of neuronal precursors due to reduced proliferation and migration compared with control mice

abnormal neuronal precursor proliferation
- reduced

decreased neuronal precursor cell number
- due to reduced proliferation and migration

Genotype: Gak^tm2Legr/Gak^tm2Legr Tg(KRT14-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA

homeostasis/metabolism phenotype

impaired skin barrier function
- at E17.5

dehydration
- shortly after birth

integument phenotype

wrinkled skin
- shortly after birth

abnormal epidermal layer morphology
- the epidermis lacks extensive differentiation and multiple cell layers compared with control mice
- the epidermis exhibits reduced neutral lipids compared with control mice

impaired skin barrier function
- at E17.5

abnormal epidermis stratum corneum morphology
- underdeveloped

mortality/aging

postnatal lethality, complete penetrance
- mice die shortly after birth

Genotype: Gak^tm2Legr/Gak^tm2Legr Tg(CAG-cre/Esr1)5Amc/0
involves: 129S6/SvEvTac C57BL/6 * CBA

mortality/aging

premature death
- mice die within six days of tamoxifen treatment

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

Genotype: Gak^tm2Legr/Gak^tm2Legr
involves: 129S6/SvEvTac * C57BL/6

cellular phenotype

abnormal plasma membrane morphology
- mouse embryonic fibroblasts treated with a cre-expressing adenovirus exhibit altered clatherin-coated pits compared with control cells

normal phenotype

no abnormal phenotype detected
- Normal - mice exhibit no phenotypic differences compared with wild-type mice

References

Lee DW; Zhao X; Yim YI; Eisenberg E; Greene LE. 2008. Essential role of cyclin-G-associated kinase (Auxilin-2) in developing and mature mice. Mol Biol Cell 19(7):2766-76PubMed: 18434600 MGI: J:180119

Additional - Gak^tm2Legr related

Technical Support

CONTACT TECHNICAL SUPPORT

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

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129S6-Gak^tm2Legr/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36793 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

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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Gaktm2Legr

Allele Symbol: Gaktm2Legr

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Gaktm2Legr/Gaktm2Legr Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+involves: 129S6/SvEvTac * C57BL/6 * DBA

endocrine/exocrine gland phenotype

mortality/aging

growth/size/body region phenotype

homeostasis/metabolism phenotype

liver/biliary system phenotype

Genotype: Gaktm2Legr/Gaktm2Legr Tg(Nes-cre)1Kln/0involves: 129S6/SvEvTac * C57BL/6 * SJL

behavior/neurological phenotype

cellular phenotype

mortality/aging

nervous system phenotype

Genotype: Gaktm2Legr/Gaktm2Legr Tg(KRT14-cre)1Amc/0involves: 129S6/SvEvTac * C57BL/6 * CBA

homeostasis/metabolism phenotype

integument phenotype

mortality/aging

Genotype: Gaktm2Legr/Gaktm2Legr Tg(CAG-cre/Esr1*)5Amc/0involves: 129S6/SvEvTac * C57BL/6 * CBA

mortality/aging

Genotype: Gaktm2Legr/Gaktm2Legrinvolves: 129S6/SvEvTac * C57BL/6

cellular phenotype

normal phenotype

References

Additional - Gaktm2Legr related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Gak^tm2Legr

Allele Symbol: Gak^tm2Legr

Genotype: Gak^tm2Legr/Gak^tm2Legr Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
involves: 129S6/SvEvTac * C57BL/6 * DBA

Genotype: Gak^tm2Legr/Gak^tm2Legr Tg(Nes-cre)1Kln/0
involves: 129S6/SvEvTac * C57BL/6 * SJL

Genotype: Gak^tm2Legr/Gak^tm2Legr Tg(KRT14-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA

Genotype: Gak^tm2Legr/Gak^tm2Legr Tg(CAG-cre/Esr1)5Amc/0
involves: 129S6/SvEvTac C57BL/6 * CBA

Genotype: Gak^tm2Legr/Gak^tm2Legr
involves: 129S6/SvEvTac * C57BL/6

Additional - Gak^tm2Legr related