JAX Mouse Strain Datasheet - 009681

C3.129S4(B6)-Mtnr1a^tm1Rep/J

Stock No:: 009681

Cryo Recovery

Overview

Mice that are homozygous for this targeted mutation of Mtnr1a, melatonin receptor 1A, do not phase shift in response to melatonin injections and have sensormotor deficits and increased depressive-like behaviors. This mutant mouse strain may be useful in studies of circadian rhythm and behavior.

Donating Investigator

David R. Weaver, Univ of Massachusetts Medical School

Genetic overview

Genetic Background	Generation

Mtnr1a^tm1Rep

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Mtnr1a	melatonin receptor 1A

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed 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). These mice are on the C3H genetic background and carry the retinal degeneration allele Pde6b^rd1. This mutant mouse strain may be useful in studies of circadian rhythm and behavior.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

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 C3H/He for 10 generations before arriving at The Jackson Laboratory. The mice were crossed to C3H/HeJ (Stock No. 000659) once to establish the colony.

Control Suggestions

000659 C3H/HeJ

Additional Information

Considerations for Choosing Controls

Selected References

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: J:41859

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Genetics

Mtnr1a^tm1Rep

Allele Symbol: Mtnr1a^tm1Rep

Allele Name	targeted mutation 1, Steven M Reppert
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	MT1 KO; MT1^-
Gene Symbol and Name	Mtnr1a, melatonin receptor 1A
Gene Synonym(s)	MEL-1A-R; MT1; Mel1a receptor; MelR
Strain of Origin	129S4/SvJae
Chromosome	8
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.
Mutations Made By	David Weaver, Univ of Massachusetts Medical School

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Behavioral and Learning Defects
- Circadian Rhythms

Mammalian Phenotype Terms by Genotype

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

Genotype: 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

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

References

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: J:41859

Additional - 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: 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: J:153084
Comai S; Ochoa-Sanchez R; Gobbi G. 2013. Sleep-wake characterization of double MT(1)/MT(2) receptor knockout mice and comparison with MT(1) and MT(2) receptor knockout mice. Behav Brain Res 243:231-8. PubMed: 23333399 MGI: J:197155
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: J:158188

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Mtnr1a<tm1Rep>

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

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Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

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In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

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The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Mtnr1atm1Rep

Allele Symbol: Mtnr1atm1Rep

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Mtnr1atm1Rep/Mtnr1atm1Repinvolves: 129S4/SvJae * C57BL/6

behavior/neurological phenotype

References

Additional - Mtnr1atm1Rep related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Mtnr1a^tm1Rep

Allele Symbol: Mtnr1a^tm1Rep

Genotype: Mtnr1a^tm1Rep/Mtnr1a^tm1Rep
involves: 129S4/SvJae * C57BL/6

Additional - Mtnr1a^tm1Rep related