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

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator David R. Weaver,   Univ of Massachusetts Medical School

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical abnormalities. No gene product (protein) binding is detected in brain by autoradiographic analysis. SCN (suprachiasma nucleus) slices from homozygous mice do not exhibit suppression of neuronal firing in response to melatonin. In vitro, melatonin at higher concentrations causes phase shifts (~4hr phase advance) suggesting another receptor can influence SCN phase. Homozygous mice do not phase shift in response to melatonin injections. Overall homozygotes do not have obvious behavioral deficits, but detailed examination reveals that homozygotes have sensormotor deficits (impaired sensorimotor gating), acoustic startle/prepulse inhibition and increases in depressive-like behaviors (spend more time floating in the Porsolt test). This mutant mouse strain may be useful in studies of circadian rhythm and behavior.

Development
A targeting vector containing a PGK-Neomycin cassette was used to disrupt exon 1. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Heterozygotes were intercrossed to generate homozygotes. The mice were then backcrossed to C57BL/6 (see SNP note below) for 10 generations before arriving at The Jackson Laboratory. The mice were crossed to C57BL/6J once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, at least 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

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

Related Strains

Strains carrying   Mtnr1a^tm1Rep allele

009681

C3.129S4(B6)-Mtnr1atm1Rep/J

View Strains carrying   Mtnr1a^tm1Rep     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Mtnr1a^tm1Rep/Mtnr1a^tm1Rep

        involves: 129S4/SvJae * C57BL/6

• behavior/neurological phenotype
• abnormal circadian rhythm
  • although circadian functions were normal, the inhibitory effect of melatonin on suprachiasma neuronal firing was abolished   (MGI Ref ID J:41859)
• • advanced circadian phase
    • phase shifting effect of melatonin on suprachiasma neuronal firing was retained in vitro although the effect was much smaller than controls at highly reduced doses of melatonin   (MGI Ref ID J:41859)

View Research Applications

Research Applications

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

Neurobiology Research
Behavioral and Learning Defects
Circadian Rhythms

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Mtnr1atm1Rep
Allele Name		targeted mutation 1, Steven M Reppert
Allele Type		Targeted (knock-out)
Common Name(s)		MT1 KO; MT1-;
Mutation Made By		David Weaver,   Univ of Massachusetts Medical School
Strain of Origin		129S4/SvJae
Gene Symbol and Name		Mtnr1a, melatonin receptor 1A
Chromosome		8
Gene Common Name(s)		MEL-1A-R; MT1; Mel1a receptor; MelR;
Molecular Note		Exon 1 was replaced with a neomycin selection cassette inserted by homologous recombination. The deleted region encoded the 5' untranslated region and the first cytoplasmic loop. Autoradiography showed an absence of melatonin binding in sections of homozygous mutant brains, indicating complete functional ablation. [MGI Ref ID J:41859]

Genotyping

Genotyping Information

Genotyping Protocols

Mtnr1a^tm1Rep, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Liu C; Weaver DR; Jin X; Shearman LP; Pieschl RL; Gribkoff VK ; Reppert SM. 1997. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron 19(1):91-102. [PubMed: 9247266]  [MGI Ref ID J:41859]

Additional References

Mtnr1a^tm1Rep related

Alcantara-Contreras S; Baba K; Tosini G. 2011. Removal of melatonin receptor type 1 increases intraocular pressure and retinal ganglion cells death in the mouse. Neurosci Lett 494(1):61-4. [PubMed: 21362461]  [MGI Ref ID J:172756]

Baba K; Pozdeyev N; Mazzoni F; Contreras-Alcantara S; Liu C; Kasamatsu M; Martinez-Merlos T; Strettoi E; Iuvone PM; Tosini G. 2009. Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor. Proc Natl Acad Sci U S A 106(35):15043-8. [PubMed: 19706469]  [MGI Ref ID J:153084]

Drazen DL; Nelson RJ. 2001. Melatonin receptor subtype MT2 (Mel 1b) and not mt1 (Mel 1a) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity. Neuroendocrinology 74(3):178-84. [PubMed: 11528219]  [MGI Ref ID J:103120]

Imbesi M; Uz T; Dzitoyeva S; Manev H. 2008. Stimulatory effects of a melatonin receptor agonist, ramelteon, on BDNF in mouse cerebellar granule cells. Neurosci Lett 439(1):34-6. [PubMed: 18501512]  [MGI Ref ID J:138555]

Jilg A; Moek J; Weaver DR; Korf HW; Stehle JH; von Gall C. 2005. Rhythms in clock proteins in the mouse pars tuberalis depend on MT1 melatonin receptor signalling. Eur J Neurosci 22(11):2845-54. [PubMed: 16324119]  [MGI Ref ID J:104310]

Jin X; von Gall C; Pieschl RL; Gribkoff VK; Stehle JH; Reppert SM; Weaver DR. 2003. Targeted disruption of the mouse Mel(1b) melatonin receptor. Mol Cell Biol 23(3):1054-60. [PubMed: 12529409]  [MGI Ref ID J:81644]

Muhlbauer E; Bazwinsky-Wutschke I; Wolgast S; Labucay K; Peschke E. 2013. Differential and day-time dependent expression of nuclear receptors RORalpha, RORbeta, RORgamma and RXRalpha in the rodent pancreas and islet. Mol Cell Endocrinol 365(2):129-38. [PubMed: 23073388]  [MGI Ref ID J:193777]

Ochoa-Sanchez R; Comai S; Lacoste B; Bambico FR; Dominguez-Lopez S; Spadoni G; Rivara S; Bedini A; Angeloni D; Fraschini F; Mor M; Tarzia G; Descarries L; Gobbi G. 2011. Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT2 Melatonin Receptor Ligand. J Neurosci 31(50):18439-18452. [PubMed: 22171046]  [MGI Ref ID J:178899]

Sengupta A; Baba K; Mazzoni F; Pozdeyev NV; Strettoi E; Iuvone PM; Tosini G. 2011. Localization of melatonin receptor 1 in mouse retina and its role in the circadian regulation of the electroretinogram and dopamine levels. PLoS One 6(9):e24483. [PubMed: 21915336]  [MGI Ref ID J:177927]

Sheynzon P; Korf HW. 2006. Targeted deletions of Mel1a and Mel1b melatonin receptors affect pCREB levels in lactotroph and pars intermedia cells of mice. Neurosci Lett 407(1):48-52. [PubMed: 16959416]  [MGI Ref ID J:112640]

Sumaya IC; Masana MI; Dubocovich ML. 2005. The antidepressant-like effect of the melatonin receptor ligand luzindole in mice during forced swimming requires expression of MT2 but not MT1 melatonin receptors. J Pineal Res 39(2):170-7. [PubMed: 16098095]  [MGI Ref ID J:114318]

Unfried C; Ansari N; Yasuo S; Korf HW; von Gall C. 2009. Impact of melatonin and molecular clockwork components on the expression of thyrotropin beta-chain (Tshb) and the Tsh receptor in the mouse pars tuberalis. Endocrinology 150(10):4653-62. [PubMed: 19589858]  [MGI Ref ID J:158141]

Weil ZM; Hotchkiss AK; Gatien ML; Pieke-Dahl S; Nelson RJ. 2006. Melatonin receptor (MT1) knockout mice display depression-like behaviors and deficits in sensorimotor gating. Brain Res Bull 68(6):425-9. [PubMed: 16459197]  [MGI Ref ID J:128633]

Yasuo S; Yoshimura T; Ebihara S; Korf HW. 2009. Melatonin transmits photoperiodic signals through the MT1 melatonin receptor. J Neurosci 29(9):2885-9. [PubMed: 19261884]  [MGI Ref ID J:158188]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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'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.

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