Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names STOCK Gprc1dtm1Hpn    (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+F6p+N1 (08-JAN-04) Generation Definitions   Donating Investigator David Hampson,   University of Toronto

Appearance
agouti
Related Genotype: unknown

Description
Metabotropic glutamate receptors are widely distributed throughout the central nervous system. Included in this group is the glutamate receptor, metabotropic 4 (also called mGluR4). The targeted gene product is found at modest levels in several areas of the CNS, but it appears to be expressed at higher levels in the granule cells of the cerebellum. No protein product is detected in the brain by immunological assays. Mutant mice appear normal in size/weight and have normal motor coordination but appear to have an impaired ability to learn complex motor tasks. The donating investigators note that these mice are selectively resistant to chemically-induced absence seizures.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying   Grm4^tm1Hpn allele

003619

B6.129-Grm4tm1Hpn/J

View Strains carrying   Grm4^tm1Hpn     (1 strain)

Strains carrying other alleles of Grm4

003619

B6.129-Grm4tm1Hpn/J

View Strains carrying other alleles of Grm4     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Grm4^tm1Hpn/Grm4^tm1Hpn

        involves: 129S1/Sv * 129X1/SvJ * CD-1

• behavior/neurological phenotype
• abnormal motor learning
  • homozygotes improve less with training in the rotating rod motor-learning test compared to wild-type mice; however performance in the open field and bar crossing tests is similar to wild-type   (MGI Ref ID J:35793)
• nervous system phenotype
• decreased paired-pulse facilitation
  • paired pulse facilitation is significantly reduced st all interstimulus intervals examined and at greater than 300msec intervals the amplitude of the second EPSC is depressed rather than facilitated as in wild-type mice   (MGI Ref ID J:35793)
  • however, long term depression is similar to wild-type   (MGI Ref ID J:35793)
• decreased post-tetanic potentiation
  • conditions that stimulate post-tetanic potentiation in wild-type mice induce only post-tetanic depression in most homozygous Purkinje cells   (MGI Ref ID J:35793)

View Research Applications

Research Applications

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

Grm4^tm1Hpn related

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Grm4tm1Hpn
Allele Name		targeted mutation 1, David R Hampson
Allele Type		Targeted (knock-out)
Common Name(s)		Gprc1dtm1Hpn; mGluR4-;
Mutation Made By		David Hampson,   University of Toronto
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Grm4, glutamate receptor, metabotropic 4
Chromosome		17
Gene Common Name(s)		GPRC1D; MGLUR4; mGlu4;
Molecular Note		A neomycin resistance cassette was inserted into an EcoRV site of an exon that encodes a region encompassing Gly 246-Arg 291 of the putative amino terminal extracellular domain of the protein. Immunoblots of cerebella from homozygous mutant mice showed no detectable protein. [MGI Ref ID J:35793]

Genotyping

Genotyping Information

Genotyping Protocols

Grm4^tm1Hpn, Separated PCR
NEOTD (Generic Neo), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Pekhletski R; Gerlai R; Overstreet LS; Huang XP; Agopyan N; Slater NT; Abramow-Newerly W; Roder JC; Hampson DR. 1996. Impaired cerebellar synaptic plasticity and motor performance in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. J Neurosci 16(20):6364-73. [PubMed: 8815915]  [MGI Ref ID J:35793]

Additional References

Bruno V; Battaglia G; Ksiazek I; van der Putten H; Catania MV; Giuffrida R; Lukic S; Leonhardt T; Inderbitzin W; Gasparini F; Kuhn R; Hampson DR; Nicoletti F; Flor PJ. 2000. Selective activation of mGlu4 metabotropic glutamate receptors is protective against excitotoxic neuronal death. J Neurosci 20(17):6413-20. [PubMed: 10964947]  [MGI Ref ID J:64207]

Grm4^tm1Hpn related

Battaglia G; Busceti CL; Molinaro G; Biagioni F; Traficante A; Nicoletti F; Bruno V. 2006. Pharmacological activation of mGlu4 metabotropic glutamate receptors reduces nigrostriatal degeneration in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurosci 26(27):7222-9. [PubMed: 16822979]  [MGI Ref ID J:110229]

Blednov YA; Walker D; Osterndorf-Kahanek E; Harris RA. 2004. Mice lacking metabotropic glutamate receptor 4 do not show the motor stimulatory effect of ethanol. Alcohol 34(2-3):251-9. [PubMed: 15902920]  [MGI Ref ID J:101929]

Bruno V; Battaglia G; Ksiazek I; van der Putten H; Catania MV; Giuffrida R; Lukic S; Leonhardt T; Inderbitzin W; Gasparini F; Kuhn R; Hampson DR; Nicoletti F; Flor PJ. 2000. Selective activation of mGlu4 metabotropic glutamate receptors is protective against excitotoxic neuronal death. J Neurosci 20(17):6413-20. [PubMed: 10964947]  [MGI Ref ID J:64207]

Fallarino F; Volpi C; Fazio F; Notartomaso S; Vacca C; Busceti C; Bicciato S; Battaglia G; Bruno V; Puccetti P; Fioretti MC; Nicoletti F; Grohmann U; Di Marco R. 2010. Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation. Nat Med 16(8):897-902. [PubMed: 20657581]  [MGI Ref ID J:163319]

Gerlai R; Roder JC; Hampson DR. 1998. Altered spatial learning and memory in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. Behav Neurosci 112(3):525-32. [PubMed: 9676970]  [MGI Ref ID J:78387]

Moritz A; Scheschonka A; Beckhaus T; Karas M; Betz H. 2009. Metabotropic glutamate receptor 4 interacts with microtubule-associated protein 1B. Biochem Biophys Res Commun 390(1):82-6. [PubMed: 19781524]  [MGI Ref ID J:155134]

Pitsch J; Schoch S; Gueler N; Flor PJ; van der Putten H; Becker AJ. 2007. Functional role of mGluR1 and mGluR4 in pilocarpine-induced temporal lobe epilepsy. Neurobiol Dis 26(3):623-33. [PubMed: 17446080]  [MGI Ref ID J:141725]

Snead OC 3rd; Banerjee PK; Burnham M; Hampson D. 2000. Modulation of absence seizures by the GABA(A) receptor: a critical rolefor metabotropic glutamate receptor 4 (mGluR4). J Neurosci 20(16):6218-24. [PubMed: 10934271]  [MGI Ref ID J:109464]

Wang X; Ai J; Hampson DR; Snead OC 3rd. 2005. Altered glutamate and GABA release within thalamocortical circuitry in metabotropic glutamate receptor 4 knockout mice. Neuroscience 134(4):1195-203. [PubMed: 16039800]  [MGI Ref ID J:104424]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	None Available
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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