Table 1.
5-HT genetic models summary.
| Genetic model | Target gene expression | Adult behavior | References | ||
|---|---|---|---|---|---|
| Embryo (%) | Early PN (%) | Adult (%) | |||
| 5-HT1A | |||||
| 5-HT1A−/− | − | – | − | Anxiety, antidepressed | Heisler et al., 1998; Parks et al., 1998; Ramboz et al., 1998 |
| 5-HT1A auto-iS (Pet1-tTX) | + | + | −30 | Antidepressed, SSRI+ | Richardson-Jones et al., 2010 |
| 5-HT1A auto-iS (Pet1-tTX) | + | −40 | + | Anxiety, social− | Donaldson et al., 2014 |
| 5-HT1A auto-iS (Pet1-tTX) | −80 | −80 | −80 | Anxiety | Richardson-Jones et al., 2011 |
| 5-HT1A hetero-iS (CamKII-tTX) | −95 | −95 | −95 | Depression | Richardson-Jones et al., 2011 |
| 5-HT1A auto-siRNA | + | + | −80 | Anti-depressed, SSRI+ | Bortolozzi et al., 2012; Ferres-Coy et al., 2013 |
| 5-HT1A hetero-rescue (CaMKII-tTA iTg) | − | + | − | Anti-anxiety | Gross et al., 2002 |
| 5-HT1A-heteroOE (5-HT1A-tg) | + | ++ | + | Anti-anxiety, Anti-depressed | Kusserow et al., 2004 |
| 5-HT1A-autoOE (Tph2-tg) | +300 | +300 | +300 | Aggression, anxiety | Audero et al., 2013; Piszczek et al., 2013 |
| 5-HT1A-auto rescue (Tph2-tg) | +300 | +300 | +300 | Anxiety, anti-depressed | Audero et al., 2013; Piszczek et al., 2013 |
| 5-HT | |||||
| TPH2−/− | − | – | − | Anti-Anxiety, depression, aggression | Mosienko et al., 2012 |
| TPH2-R439H KI | −80 | −80 | −80 | Anxiety, depression | Jacobsen et al., 2012b; Sachs et al., 2013 |
| PET1−/− | −80 | −80 | −80 | Aggression, anxiety | Hendricks et al., 2003 |
| Pet1-adult-iKO | + | + | −80 | Anxiety | Liu et al., 2010 |
| En1/Pet1-TetTX IT | −* | −* | −* | Anti-Anxiety, cognitive+ | Kim et al., 2009 |
| 5-HTT | |||||
| 5-HTT-/- | − | – | − | Anxiety, depression anti-aggression | Holmes et al., 2002, 2003; Lira et al., 2003; Kalueff et al., 2006 |
| 5-HTT-FLX | + | − | + | Anxiety | Ansorge et al., 2004 |
| 5-HTT-G56A KI | ++* | ++* | ++* | Social−, SSRI+ | Veenstra-Vanderweele et al., 2012 |
| 5-HTT-tg | +100 | +100 | +100 | Anti-anxiety | Jennings et al., 2006 |
Genetic models are as defined in Box 1 with promoter used indicated in parentheses; rescue is expression in knockout background, over-expression (OE) is on wild-type background; auto, autoreceptor-specific; hetero, heteroreceptor-specific. The effect of the indicated genetic model on target gene expression (−, none; +, normal; ++, increased; +X, increased by X%) at indicated developmental time [embryo, early post-natal (PN) or adult] and adult behavior phenotype or response to SSRI are indicated.
*
loss of 5-HT release; enhanced activity 5-HTT mutant.