Synaptotagmin10-Cre, a driver to disrupt clock genes in the SCN

J Biol Rhythms. 2011 Oct;26(5):379-89. doi: 10.1177/0748730411415363.

Abstract

Surgical lesion of the suprachiasmatic nuclei (SCN) profoundly affects the circadian timing system. A complication of SCN ablations is the concomitant scission of SCN afferents and efferents. Genetic disruption of the molecular clockwork in the SCN provides a complementary, less invasive experimental approach. The authors report the generation and functional analysis of a new Cre recombinase driver mouse that evokes homologous recombination with high efficiency in the SCN. They inserted the Cre recombinase cDNA into the Synaptotagmin10 (Syt10) locus, a gene strongly expressed in the SCN. Heterozygous Synaptotagmin10-Cre (Syt10(Cre)) mice have no obvious circadian locomotor phenotype, and homozygous animals show slightly reduced light-induced phase delays. Crosses of Syt10(Cre) mice with β-galactosidase reporter animals revealed strong Cre activity in the vast majority of SCN cells. Cre activity is not detected in nonneuronal tissues with the exception of the testis. The authors demonstrate that conditionally deleting the clock gene Bmal1 using the Syt10(Cre) driver renders animals arrhythmic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / physiology
  • Animals
  • Behavior, Animal
  • CLOCK Proteins / genetics*
  • Circadian Rhythm / genetics*
  • Circadian Rhythm / physiology
  • Gene Knock-In Techniques
  • Homologous Recombination
  • Integrases / genetics*
  • Male
  • Mice
  • Motor Activity / genetics
  • Suprachiasmatic Nucleus / physiology*
  • Synaptotagmins / genetics
  • Synaptotagmins / physiology*
  • beta-Galactosidase / genetics

Substances

  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Syt10 protein, mouse
  • Synaptotagmins
  • CLOCK Proteins
  • Cre recombinase
  • Integrases
  • beta-Galactosidase