Gong, S, Doughty, M, Harbaugh, CR, Cummins, A, Hatten, ME, Heintz, N et al.. Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs. J Neurosci 27: 9817-9823
Transgenic mouse lines are characterized with Cre recombinase driven by promoters of CNS-specific genes using bacterial artificialchromosome (BAC) constructs. BAC-Cre constructs for 10 genes (Chat, Th, Slc6a4, Slc6a2, Etv1, Ntsr1, Drd2, Drd1, Pcp2, and Cmtm5)produced 14 lines with Cre expression in specific neuronal and glial populations in the brain. These Cre driver lines add functional utility to the >500 BAC-EGFP (enhanced green fluorescent protein) transgenic mouse lines that are part of the Gene Expression Nervous System Atlas Project.
"Results obtained with the GFP reporter mouse line show that the GM60 line targets more efficiently and selectively cholinergic neurons in corticopetal BF nuclei and striatum than in hippocampopetal medial septal nucleus and neocortex . The BAC used to generate the GM60 Cre line contains the first intron of the ChAT gene, thus also the vesicular ACh transporter gene (Bejanin et al. 1994; Roghani et al. 1994; Gong et al. 2007). Nonetheless, currents we measured in non-cre mice with same genetic background (α5−/− line) provided no evidence for enhanced nicotinic transmission in the GM60 line, in contrast with the hypercholinergic phenotype reported for another BAC-based ChAT-ChR2-YFP transgenic mouse line (Kolisnyk et al. 2013). "
"To observe and manipulate their activities selectively, the best available approach is genetic targeting of protein-based sensors and effectors to specific cell types (Huang and Zeng, 2013). In mice, the Cre/lox recombination system is the most widely used approach to access specific cell types, utilizing gene promoters or loci with specific expression patterns (Gerfen et al., 2013; Gong et al., 2007; Madisen et al., 2010; Taniguchi et al., 2011). However, cell populations defined by Cre driver lines are often heterogeneous, encompassing multiple brain regions and/or multiple cell types (Harris et al., 2014). "
"The development and genotyping of the 5-HT Oxtr KO is similar to that of the forebrain Oxtr line (Lee et al. 2008): the conditional Oxtr KO line (B6.129(SJL)-Oxtr tm1.1Wsy /J) is crossed with a transgenic line expressing Cre recombinase under the control of serotonin transporter [Tg(Slc6a4-cre)ET33Gsat, originally on FVB/N background; generously provided by Charles Gerfen, NIMH; Gong et al. 2007]. In this line, the Slc6a4 promoter drives Cre recombinase expression in serotonergic neurons (Fig. 1, for dorsal and MR expression ). "
[Show abstract][Hide abstract] ABSTRACT: Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically-mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to eight of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care.
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