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

Stock number: 009681
Research areas: Neurobiology Research

Description

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.

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.

Allele

Symbol: Mtnr1a^tm1Rep
Name: targeted mutation 1, Steven M Reppert
MGI accession ID: MGI:2450160
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: MT1 KO; MT1^-
Marker symbol: Mtnr1a
Marker name: melatonin receptor 1A
Marker synonyms: Mel1a receptor; MEL-1A-R; MelR; MT1
Chromosome: 8
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.