Induction of γ-globin mRNA by short-chain fatty acid derivatives in transgenic mice
| Animal . | Compound tested . | Baseline (γ/γ + β) . | Treatment (γ/γ + β) . | Fold increase . | P value . |
|---|---|---|---|---|---|
| W1P | AMHCA | 0.33 | 0.81 | 2.5 | .04 |
| W2P | AMHCA | 0.14 | 0.21 | 1.5 | .02 |
| 8618 | AMHCA | 0.03 | 0.10 | 3.3 | .05 |
| W2P | DMB | 0.17 | 0.36 | 2.1 | .03 |
| W1P | DMB | 0.05 | 0.08 | 1.6 | .04 |
| 1-1P | PAA | 0.23 | 0.42 | 1.8 | .02 |
| 5-3P | PAA | 0.40 | 0.80 | 2.0 | .01 |
| 7-1P | PAA | 0.30 | 0.71 | 2.4 | .03 |
| 3638 | SB | 0.07 | 0.12 | 1.7 | .05 |
| 8633 | SB | 0.06 | 0.13 | 2.2 | .03 |
| 8636 | SB | 0.10 | 0.19 | 1.9 | .03 |
| Animal . | Compound tested . | Baseline (γ/γ + β) . | Treatment (γ/γ + β) . | Fold increase . | P value . |
|---|---|---|---|---|---|
| W1P | AMHCA | 0.33 | 0.81 | 2.5 | .04 |
| W2P | AMHCA | 0.14 | 0.21 | 1.5 | .02 |
| 8618 | AMHCA | 0.03 | 0.10 | 3.3 | .05 |
| W2P | DMB | 0.17 | 0.36 | 2.1 | .03 |
| W1P | DMB | 0.05 | 0.08 | 1.6 | .04 |
| 1-1P | PAA | 0.23 | 0.42 | 1.8 | .02 |
| 5-3P | PAA | 0.40 | 0.80 | 2.0 | .01 |
| 7-1P | PAA | 0.30 | 0.71 | 2.4 | .03 |
| 3638 | SB | 0.07 | 0.12 | 1.7 | .05 |
| 8633 | SB | 0.06 | 0.13 | 2.2 | .03 |
| 8636 | SB | 0.10 | 0.19 | 1.9 | .03 |
The γ-globin mRNA in mice transgenic for the LCR and the entire human β-globin gene locus in a yeast artificial chromosome. Mice were treated with SB 1000 mg/kg/d continuously for 7 days or with 1 of 3 prototype SCFADs (AMHCA, DMB, PAA) given in aqueous solutions at neutral pH as intraperitoneal injections once daily for 5 or 7 days. Doses of the SCFADs were 500/mg/kg, except for animal 1-1P, which received 1000/mg/kg for 1 day and 500/mg/kg for 4 days, and animal 7-1P, which received daily doses of 250/mg/kg for 5 days. Baseline and 3 peak on-treatment γ-globin mRNA levels were compared using repeated measures analysis of variance.
AMHCA indicates α-methylhydrocinnamic acid; DMB, dimethylbutyric acid; PAA, phenoxyacetic acid; SB, sodium butyrate; SCFAD, short-chain fatty acid derivative; LCR, locus control region.