Table 1. 5-HT Relevant Factors in Humans Associated with ASD, and Analogous Mouse Models of Genetic or Environmental Conditions.
All factors listed in the table have an association with ASD in humans. Genetic or environmental manipulation of these factors in mouse models either demonstrate social behavior deficits, repetitive behaviors, both, or in the case of NSF has yet to be tested in a mouse model.
| Genetic Polymorphisms |
Functional Outcome |
Human Reference |
Mouse Model |
Social Deficits |
Repetitive Behaviors |
Model Reference |
|---|---|---|---|---|---|---|
| 5-HTTLPR | ||||||
| SLC6A4 S/S | hypofunctional SERT uptake | [93] | KO | ✓ | [88,94] | |
| SLC6A4 S/L | hypofunctional SERT uptake | [21,95] | HET | ✓ | [96] | |
| SLC6A4 Gly56Ala | hyperfunctional SERT uptake | [24] | Ala56 | ✓ | ✓ | [79,97] |
| TPH | ||||||
| TPH2: introns | decreased 5-HT synthesis | [52,70] | KO | ✓ | ✓ | [82,78,98] |
| MAO | ||||||
| MAOA | decreased 5-HT metabolism | [73,74,76] | KO | ✓ | ✓ | [84,86] |
| MAOB | decreased 5-HT metabolism | [76,99] | KO | ✓ | ✓ | [85,86] |
| Proteins | ||||||
| αIIbβ3 | decreased SERT expression | [100,101] | KO | ✓ | ✓ | [102] |
| NSF | decreased SERT expression | [101,103] | KD | NE | NE | [103] |
|
Environmental Factors |
||||||
| TRP Reduction | decreased 5-HT synthesis | [104,105] | dietary reduction | [106] |
*
Knock-out (KO), knock-down (KD), heterozygote (HET), not examined (NE) (behavioral tests have not been conducted with the N-ethylmaleimide-sensitive factor (NSF) KD mouse), integrin alphaIIbbeta3 transmembrane complex (αIIbβ).