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. 2015 Jul 15:4:718.
doi: 10.1038/bonekey.2015.87. eCollection 2015.

Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low cortical bone thickness

Robert Brommage  1 , Jeff Liu  1 , Deon Doree  1 , Wangsheng Yu  1 , David R Powell  1 , Qi Melissa Yang  1
Affiliations

Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low cortical bone thickness

Robert Brommage et al. Bonekey Rep. .

Abstract

Disruption of serotonin synthesis in neurons and the periphery by knockout (KO) of mouse genes for tryptophan hydroxylases (peripheral Tph1 and neuronal Tph2) has been claimed to decrease (Tph2 KO) and increase (Tph1 KO) bone mass. In this report, adult male and female Tph2 KO mice were observed to have elevated spine trabecular bone. Female Tph2 KO mice have reduced midshaft femur cortical bone thickness. Bone mass was normal in male and female Tph1 KO mice examined as part of a Tph1/Tph2 double knockout (DKO) mouse cohort.

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Conflict of interest statement

Lexicon Pharmaceuticals is currently examining a drug (telotristat etiprate) inhibiting TPH1 in a Phase III clinical trial for carcinoid syndrome. All authors were full-time employees of Lexicon Pharmaceuticals when the experiments were performed.

Figures

Figure 1
Figure 1
Brain, whole blood and jejunal serotonin contents in Tph1 KO, Tph2 KO and Tph1/Tph2 DKO mice. Male mice were examined at 33 weeks of age.
Figure 2
Figure 2
Urinary 5-HIAA excretion for Tph1 and Tph2 KO mice. Male Tph1 KO mice studied at 14 months of age (left) and female Tph2 KO mice at 6–7 months of age (right). Tph1 KO mouse data were published previously. Data are means±s.e.m. for six mice per group. For Tph1 KO mice, P<0.001 for Days 1, 2, 3 and 4. For Tph2 KO mice, P<0.01 for days 1, 2 and 4.
Figure 3
Figure 3
Body weight during growth in Tph2 KO mice. Data obtained during high-throughput screening. Equal numbers of male and female mice were examined for each genotype at each age, with Ns=4 for WT and Ns=8 for KO mice. P<0.001 at 2 weeks and P=0.02 at 4 weeks of age.
Figure 4
Figure 4
MicroCT bone data for Tph1 KO, Tph2 KO and Tph1/Tph2 DKO mice. Male (top) and female (bottom) mice were examined at 21 and 83 weeks of age, respectively.
Figure 5
Figure 5
Tph1 (exons 4 through 7) KO strategy.
See this image and copyright information in PMC

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