Strain Name:

B6.129(Cg)-Homer1tm1Mhd/PfwJ

Stock Number:

023312

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Availability:

Under Development - Now Accepting Orders

Estimated Available for Distribution Date: 11-AUG-14
Use Restrictions Apply, see Terms of Use
These Homer1 KO mice may be useful for studying the role of HOMER1 on behavioral and neurochemical defects.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemWild-type x Heterozygote         (Female x Male)   19-FEB-14
Mating SystemHeterozygote x Wild-type         (Female x Male)   19-FEB-14
Specieslaboratory mouse
 
Donating Investigator Paul Worley,   Johns Hopkins University School of Medic

Description
These Homer1 KO mice lack exon 2 of homer homolog 1 (Homer1) gene, abolishing gene expression. HOMER1 is a postsynaptic density scaffolding protein expressed in the central nervous system, as well as skeletal muscle, where it mediates the formation of large macromolecular complexes and regulates group 1 metabotrophic glutamate receptor function. Mice that are homozygous for this allele are viable and fertile. These mice exhibit myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. They display mild somatic growth retardation, poor motor coordination, enhanced sensory reactivity and learning deficits, and an increase in sensitivity to cocaine-induced locomotion and conditioned reward. They also display behavioral and neurochemical abnormalities consistent with the schizophrenia including decreased radial arm maze performance, impaired prepulse inhibition, enhanced behavioral despair, increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced methamphetamine-stimulated motor behavior.

Development
A targeting vector was designed to insert a single loxP site upstream of exon 2, and a second loxP site, followed by a frt-flanked neomycin resistance (neo) cassette, downstream of exon 2 of the homer homolog 1 (Homer1) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6 mice. Offspring were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 005703) to delete the neo cassette, and subsequently bred to B6.C-Tg(CMV-cre)1Cgn/J transgenic mice (Stock No. 006054) to delete exon 2. Progeny were crossed to remove the Flp and cre-expressing transgenes. These mice were bred to C57BL/6J mice for at least 5 generations. These mice also carried a Homer2tm1Mhw KO allele. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony. The Homer2tm1Mhw was bred out and is maintained separately as Stock No. 023313.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Homer1tm1Mhd/Homer1tm1Mhd

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6
  • endocrine/exocrine gland phenotype
  • abnormal pancreas physiology
    • ~2.5-fold increase in spontaneous calcium influx in acinar cells compared to wild-type   (MGI Ref ID J:95212)
    • depletion of calcium stores in homozygous mutant acinar cells further increased calcium influx by only 1.7 fold compared to 3.2-fold in wild-type   (MGI Ref ID J:95212)
    • increase in the ratio of spontaneous to store-depletion current (59% compared to 26% in wild-type) in acinar cells   (MGI Ref ID J:95212)

Homer1tm1Mhd/Homer1tm1Mhd

        involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6
  • behavior/neurological phenotype
  • enhanced behavioral response to cocaine
    • capacity of acute cocaine to elicit locomotor hyperactivity is enhanced in mutants compared to controls   (MGI Ref ID J:96554)
  • enhanced conditioned place preference behavior
    • mutants exhibit cocaine-induced place conditioning compared to wild-type controls   (MGI Ref ID J:96554)
    • mice exhibit cocaine-induced place conditioning (increased time spent in environment containing stimulus/reward) at doses that do not elicit place conditioning in controls   (MGI Ref ID J:96554)
    • mice prefer to spend more time in chamber where cocaine is available compared to controls   (MGI Ref ID J:96554)
  • nervous system phenotype
  • abnormal nervous system physiology
    • mutants show lower (~50%) extracellular glutamate levels in the nucleus accumbens compared to wild-type mice; injection of cocaine into the nucleus accumbens causes elevation of extracellular glutamate levels in mutants but not wild-type controls   (MGI Ref ID J:96554)
View Research Applications

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

Neurobiology Research
Behavioral and Learning Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Homer1tm1Mhd
Allele Name targeted mutation 1, Marlin H Dehoff
Allele Type Targeted (knock-out)
Common Name(s) H1ko;
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Homer1, homer homolog 1 (Drosophila)
Chromosome 13
Gene Common Name(s) HOMER; HOMER1A; HOMER1B; HOMER1C; HOMER1F; PSD-Zip45; SYN47; Ves-1; Vesl-1;
Molecular Note One loxP site was inserted 200 bp upstream of exon 2 and an SV40-neo cassette flanked with frt sites and containing an additional loxP site was inserted 700 bp downstream of exon 2. The neomycin insert was subsequently removed by crossing to Flpe transgenic mice after which exon 2 was excised by crossing to CMV-cre transgenic mice. [MGI Ref ID J:95212]

Genotyping

Genotyping Information

Genotyping Protocols

Homer2tm1Mhd-Alternate 1, Standard PCR
Homer3tm1Mhd-Alternate 1, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yuan JP; Kiselyov K; Shin DM; Chen J; Shcheynikov N; Kang SH; Dehoff MH; Schwarz MK; Seeburg PH; Muallem S; Worley PF. 2003. Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 114(6):777-89. [PubMed: 14505576]  [MGI Ref ID J:95212]

Additional References

Homer1tm1Mhd related

Huang G; Kim JY; Dehoff M; Mizuno Y; Kamm KE; Worley PF; Muallem S; Zeng W. 2007. Ca2+ signaling in microdomains: Homer1 mediates the interaction between RyR2 and Cav1.2 to regulate excitation-contraction coupling. J Biol Chem 282(19):14283-90. [PubMed: 17355963]  [MGI Ref ID J:122552]

Huang GN; Huso DL; Bouyain S; Tu J; McCorkell KA; May MJ; Zhu Y; Lutz M; Collins S; Dehoff M; Kang S; Whartenby K; Powell J; Leahy D; Worley PF. 2008. NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins. Science 319(5862):476-81. [PubMed: 18218901]  [MGI Ref ID J:174501]

Jaubert PJ; Golub MS; Lo YY; Germann SL; Dehoff MH; Worley PF; Kang SH; Schwarz MK; Seeburg PH; Berman RF. 2007. Complex, multimodal behavioral profile of the Homer1 knockout mouse. Genes Brain Behav 6(2):141-54. [PubMed: 16734773]  [MGI Ref ID J:122723]

Kuwajima M; Dehoff MH; Furuichi T; Worley PF; Hall RA; Smith Y. 2007. Localization and expression of group I metabotropic glutamate receptors in the mouse striatum, globus pallidus, and subthalamic nucleus: regulatory effects of MPTP treatment and constitutive Homer deletion. J Neurosci 27(23):6249-60. [PubMed: 17553998]  [MGI Ref ID J:121962]

Lominac KD; Oleson EB; Pava M; Klugmann M; Schwarz MK; Seeburg PH; During MJ; Worley PF; Kalivas PW; Szumlinski KK. 2005. Distinct roles for different Homer1 isoforms in behaviors and associated prefrontal cortex function. J Neurosci 25(50):11586-94. [PubMed: 16354916]  [MGI Ref ID J:103995]

Park JM; Hu JH; Milshteyn A; Zhang PW; Moore CG; Park S; Datko MC; Domingo RD; Reyes CM; Wang XJ; Etzkorn FA; Xiao B; Szumlinski KK; Kern D; Linden DJ; Worley PF. 2013. A prolyl-isomerase mediates dopamine-dependent plasticity and cocaine motor sensitization. Cell 154(3):637-50. [PubMed: 23911326]  [MGI Ref ID J:200071]

Stiber JA; Zhang ZS; Burch J; Eu JP; Zhang S; Truskey GA; Seth M; Yamaguchi N; Meissner G; Shah R; Worley PF; Williams RS; Rosenberg PB. 2008. Mice lacking Homer 1 exhibit a skeletal myopathy characterized by abnormal transient receptor potential channel activity. Mol Cell Biol 28(8):2637-47. [PubMed: 18268005]  [MGI Ref ID J:133899]

Szumlinski KK; Dehoff MH; Kang SH; Frys KA; Lominac KD; Klugmann M; Rohrer J; Griffin W rd; Toda S; Champtiaux NP; Berry T; Tu JC; Shealy SE; During MJ; Middaugh LD; Worley PF; Kalivas PW. 2004. Homer proteins regulate sensitivity to cocaine. Neuron 43(3):401-13. [PubMed: 15294147]  [MGI Ref ID J:96554]

Szumlinski KK; Lominac KD; Kleschen MJ; Oleson EB; Dehoff MH; Schwarz MK; Seeburg PH; Worley PF; Kalivas PW. 2005. Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia. Genes Brain Behav 4(5):273-88. [PubMed: 16011574]  [MGI Ref ID J:114304]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemWild-type x Heterozygote         (Female x Male)   19-FEB-14
Heterozygote x Wild-type         (Female x Male)   19-FEB-14

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 11-AUG-14

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Homer1tm1Mhd  
$232.00Female or MaleHomozygous for Homer1tm1Mhd  
Price per Pair (US dollars $)Pair Genotype
$464.00Heterozygous for Homer1tm1Mhd x Heterozygous for Homer1tm1Mhd  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Homer1tm1Mhd  
$301.60Female or MaleHomozygous for Homer1tm1Mhd  
Price per Pair (US dollars $)Pair Genotype
$603.20Heterozygous for Homer1tm1Mhd x Heterozygous for Homer1tm1Mhd  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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