Types of animals used in TNU
We use outbred wild-type mice and rats , and also breed special strains of mice and rats ourselves (TRAP2, SERT, TPH1/2, DRD1, TH-Cre, TPH2-Cre, EHMT1).
Long Evans rats are outbred white rats with a black or brown hood and a dark stripe on their back. These rats are a general multipurpose model ideal for behavioural research, learning paradigms, addiction and metabolic studies. Lister Hooded rats are outbred rats with a docile disposition. This particular strain is susceptible to audiogenic seizures. We also use black-6 mice, which are outbred.
Some of the special strains
Targeted Recombination in Active Populations (TRAP) mice
This transgenic mouse line allows the researchers to fluorescently label populations of neurons that are activated over a certain period of time. It is currently thought that each experience (e.g. memory) is represented by those neurons that are activated during learning across different brain regions. By using the TRAP mice, researchers can investigate memory representations in the brain.
Serotonin transporter knock-out (SERT KO) rats
SERT KO rats are obtained through ENU-driven target selected mutagenesis. In homozygous knockout rats (SERT -/-), a functional SERT protein is absent, leading to a significant increase in extracellular serotonin. Other monoaminergic systems remain intact, thus the neurochemical changes are limited to the serotonergic system. This makes this particular rat model valuable in studying behavioral and biological effects of serotonin disturbances.
Tryptophan Hydroxylase (TPH) 1 and 2 knock-out (TPH 1- KO) (TPH 2 - KO) rats
These TPH1 and TPH 2 animals display a significant reduction in tryptophan hydroxylase (TPH), which is a rate limiting enzyme involved in serotonin synthesis as it catalyzes 5-hydroxytryptophan to serotonin. This particular enzyme comes in two isoforms; TPH1 and TPH2. The main difference between the TPH1 and TPH 2 knockout models is that TPH1 KO animals have an overall reduction in the serotonin synthesis throughout the entire body, while TPH 2 KO animals have a reduced serotonin synthesis within the brain.
Dopamine D1 Receptor (DRD1)
This is a rat model, obtained through ENU-driven target selected mutagenesis, which has a genetic mutation in the dopamine receptor. In this model, there is a reduction in transmembrane dopamine D1 receptors, which has downstream effects on social behaviour (such as a strong reduction in social interaction, scent marking and socialbility). This rat model is particularly useful in studying psychiatric disorders such as schizophrenia, autism and drug addiction.
Tyrosine Hydroxylase - Cre Recombinase knock-in (TH-Cre) mice
In this model, the Tyrosine Hydroxylase promoter directs expression of cre-recombinase in dopaminergic neurons. The TH-cre mouseis useful for applications requiring tissue specific expression, such as optogenetic manipulation of particular cell types. In addition, they are also used in generating Cre-Lox animal models, which allows for a very targeted control of gene expression, in particular cell types.
Tryptophan Hydroxylase 2 (TPH 2) - Cre recombinase rats: this particular models enables specific expression of serotonergic neurons containing TPH 2 and ise useful in optogenetic manipulations and breeding with transgenic floxed lines.
Euchromatin Histone Methyltransferase 1 (EHMT 1 + /- ) mice
These mice have a particular deletion of the EMHT 1 gene, which is at the heart of the Kleefstra syndrome, which encompasses moderate to severe intellectual disability, hyperactivity and autistic like features. EHMT +/- mice also display such traits, ranging from diminished social play, to learning and memory deficits and hyperactive behaviour. Through the use of this model, researchers can elucidate the underlying mechanisms of EHMT deletion.