STOCK Sim1^tm1.2Az/J

Stock number: 007570
Research areas: Neurobiology Research, Research Tools

Description

These "Sim1-floxed exon 1" (2-loxP) mice may be useful in generating conditional mutations for studying basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) transcription factors, central nervous system development, early-onset/hyperphagic obesity, and regulation of appetite and energy balance.

Detailed description

Mice homozygous for this "Sim1-floxed exon 1" (2-loxP) conditional allele are viable and fertile, with loxP sites flanking the translation start site and the first 17 amino acids of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have this region (coding for the basic domain of SIM1) deleted in the cre-expressing tissue(s). These "Sim1-floxed exon 1" (2-loxP) mice may be useful in generating conditional mutations for studying basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) transcription factors, central nervous system development, early-onset/hyperphagic obesity, and regulation of appetite and energy balance.

Development

A targeting vector was designed to place a loxP site just upstream of the ATG translational start site and a loxP-flanked PGK-Neo cassette downstream of the same exon of the targeted gene. In the primary publication, a theoretical first exon preceded the exon containing the Sim1 ATG start site. The donating investigator reports that the theoretical first exon is no longer considered to represent a functional exon). The targeting construct was electroporated into 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Chimeric mice were bred to C57BL/6 mice to generate heterozygous "three-loxP" mice. Next, the neomycin selection cassette was excised by crossing to FVB transgenic mice with widespread Cre recombinase expression (see Stock No. 003314). The resulting offspring harboring the "floxed exon 1" (2-loxP) conditional allele (loxP-flanked exon 1 with PGK-neo removed) were intercrossed and then maintained as a homozygous colony prior to arrival at The Jackson Laboratory. Upon arrival, mice may have been bred to C57BL/6J for at least one generation to establish the colony.

Allele

Symbol: Sim1^tm1.2Az
Name: targeted mutation 1.2, Andrew R Zinn
MGI accession ID: MGI:3758479
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Sim1
Marker name: single-minded family bHLH transcription factor 1
Chromosome: 10
Strain of origin: 129X1/SvJ
Molecular note: A targeting vector was designed to place a loxP site just upstream of the ATG translational start site and a loxP-flanked PGK-Neo cassette downstream of the same exon of the targeted gene. The construct was injected into RW-4 ES cells. Chimeric mice were bred to C57BL/6 mice, and the neomycin selection cassette was excised from these mice by crossing to FVB transgenic mice with widespread Cre recombinase expression.