B6.Cg-Tg(Per1-luc)025Jt/J

Stock number: 006851
Research areas: Neurobiology Research, Research Tools

Description

These mPer1-luc transgenc mice may be useful in studying circadian rhythms and as a real-time reporter of Per1 expression.

Detailed description

Mice hemizygous for the "mPer1-Luc" transgene are viable and fertile, with luciferase (luc) expression driven by the mouse Per1 promoter and 5'-UTR elements. Expression of luc RNA is highly specific to the suprachiasmatic nuclei (SCN) with a clear circadian rhythm that correlates with endogenous Per1. Slice cultures taken from hemizygous mice maintain a circadian rhythm of luminescence for at least 5 days after culturing. A prolonged (6 hour) light pulse treatment during the subjective night rapidly induces both mPer1-luc and endogenous mRNA expression; while the endogenous mRNA level decreased to baseline during the 6 hour period, the mPer1-luc mRNA levels remain higher. These mPer1-luc transgenc mice may be useful in studying circadian rhythms and as a real-time reporter of Per1 expression.

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. As the original publication describes mice on a STOCK genetic background, it should be noted that the phenotype could vary from that originally described. The donating investigator reports that no segregating phenotypic traits are observed on the C57BL/6 congenic background. We will modify the strain description if necessary as published results become available.

Development

This "mPer1-luc" transgene was designed with the firefly luciferase gene (luc) downstream of a 6.7 kbp sequence from the period homolog 1 (Per1) promoter and 5'-UTR sequence. This was engineered such that the Per1 initiator ATG coincided with the luciferase initiator ATG. This construct was microinjected into CD1 mouse embryos. Transgenic offspring (founder line P1L025) were found to have approximately 10 tandem repeats at a single integration site. This line was maintained on the CD1 outbred background. After this, transgenic mice were backcrossed to C57BL/6 for 5 generations prior to arriving at The Jackson Laboratory.

Allele

Symbol: Tg(Per1-luc)025Jt
Name: transgene insertion 025, Joseph S Takahashi
MGI accession ID: MGI:3578413
Generation method: Transgenic
Attributes: Reporter
Marker symbol: Tg(Per1-luc)025Jt
Marker name: transgene insertion 025, Joseph S Takahashi
Chromosome: UN
Strain of origin: CD-1
Expressed genes: luc,luciferase,firefly
Site of expression: suprachiasmatic nuclei (SCN) with a clear circadian rhythm
Molecular note: A 6,756-base pair DNA fragment containing the putative promoter sequence and the 5'-untranslated region, which encompasses exon 1 and part of exon 2, was ligated to the luciferase gene so that the initiating ATGs of the Per1 and luc genes coincided.
General note: 6 transgenic lines were generated and designated by the authors P1L005 (2 copies/genome), P1L025 (1 copy), P1L095 (3), P1L097 (1), P1L128 (2) and P1L141 (10). Brain sections of mice of line Tg(Per1-luc)025Jt (P1L025) were hybridized with luc and Per1 probes to verify the ability of the promoter to maintain a normal circadian pattern of expression after seven days in constant darkness. As results of other experiments were similar for all six lines, data were not differentiated by line.

Mice hemizygous for the transgene express luc mRNA in the suprachiasmatic nuclei (SCN) with a circadian rhythm. SCN slice cultures exhibit a circadian rhythm of luminescence for at least 5 days, peaking each day at 6 hours circadian time. Exposure of mice to light for 6 hours during early subjective night rapidly induces transcription of both luc and endogenous Per1 in the SCN; however, whereas Per1 mRNA levels return to baseline, luc mRNA levels remain high.