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.
David R. Weaver, Univ of Massachusetts Medical School
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.
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.
|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|
|Strain of Origin||129S4/SvJae|
|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
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129S4-Mtnr1atm1Rep/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010561 in your Materials and Methods section.