Insulin sensitivity in LTKO mice fed chow diet.

<p>(A) Insulin tolerance tests (ITT) in 3-month male control and LTKO mice (n=6) after 3-hour fasting and an intraperitoneal injection of 0.75 U human regular insulin (humulin R, Lilly) per kg body weight. (B) The data in Panel A were replotted as percentage of basal blood glucose as a function of injection time. (C) Plasma insulin levels in 4-month male control and LTKO mice (n=12) after an overnight 16-hour fasting. (D) Plasma insulin levels in 4-month male control and LTKO mice (n=6) under <i>ad libitum</i> conditions. Data represent mean ± SEM. * indicates a significance with <i>P</i><0.05 in control vs. LTKO mice.</p

Sirt6 overexpression has no significant effect on glucose toerance in LTKO mice.

<p>(A) Sirt6 overexpression was assessed by Western blot analysis in liver lysates from control and LTKO mice injected with SIRT6 or GFP adenoviruses (n=6). (B) Glucose tolerance tests in 4-month-old control and LTKO mice injected with SIRT6 or GFP adenoviruses (n=6). (C) Expression of genes involved in glucose metabolism was analyzed in the livers of SIRT6 or GFP adenovirus infected control and LTKO mice (n=6) by real-time PCR. Data represent mean ± SEM. * indicates a significance with <i>P</i><0.05 between loxp-GFP and loxp-SIRT6 groups.</p

Gck knockdown impairs glucose tolerance in both wild-type and LTKO mice.

<p>(A) Gck protein was analyzed in the livers of 3-month-old control and LTKO mice by Western blots. (B) Gck knockdown was assessed by Western blots in liver lysates from control and LTKO mice injected with shGck or shGFP adenoviruses. (C, D) Glucose tolerance tests and insulin tolerance tests in 6-month-old male control and LTKO mice injected with shGck or shGFP adenoviruses (n=5-6), respectively. Data represent mean ± SEM. *, <i>P</i><0.05 between LTKO-shGFP and LTKO-shGck groups; #, <i>P</i><0.05 between loxp-shGFP and loxp-shGck groups.</p

LTKO mice maintain euglycemic and glucose tolerant on a high-fat diet.

<p>(A) Fasting glucose levels in 4.5-month male control and LTKO mice (n=8) after the treatment with a high-fat diet for 3.5 months. (B) Non-fasting blood glucose levels in 4-month male control and LTKO mice (n=8) after the treatment with the high-fat diet for 3 months. (C, D) Glucose tolerance tests and the AUC analysis in 4.5-month male control and LTKO mice (n=8) after the treatment with the high-fat diet for 3.5 months, respectively. (E, F) Expression of genes involved in glucose metabolism was analyzed in the liver of control and LTKO mice (n=4) treated with the high-fat diet for 5 months by real-time PCR. <i>Pck1</i>, phosphoenoylpyruvate carboxykinase 1; <i>G6pc</i>, glucose-6-phosphatase, catalytic; <i>Pdk2</i>, pyruvate dehydrogenase kinase 2; <i>Gck</i>, glucokinase; <i>Pklr</i>, pyruvate kinase, liver and red blood cell type. Data represent mean ± SEM. * indicates a significance with <i>P</i><0.05 in control vs. LTKO mice.</p

Body composition of LTKO mice fed a high-fat diet.

<p>(A, B) Body weight and length measurements of control and LTKO mice (n=6) after a high-fat diet (HFD) treatment for 5 months, respectively. (C, D) Body fat and bone mineral density (BMD) analyses of the above HFD treated mice by DEXA, respectively. Data represent mean ± SEM.</p

Optochemogenetics (OCG) Allows More Precise Control of Genetic Engineering in Mice with CreER regulators

New approaches that allow precise spatiotemporal control of gene expression in model organisms at the single cell level are necessary to better dissect the role of specific genes and cell populations in development, disease, and therapy. Here, we describe a new optochemogenetic switch (OCG switch) to control CreER/loxP-mediated recombination via photoactivatable (″caged″) tamoxifen analogues in individual cells in cell culture, organoid culture, and <i>in vivo</i> in adult mice. This approach opens opportunities to more fully exploit existing CreER transgenic mouse strains to achieve more precise temporal- and location-specific regulation of genetic events and gene expression

Optochemogenetics (OCG) Allows More Precise Control of Genetic Engineering in Mice with CreER regulators

New approaches that allow precise spatiotemporal control of gene expression in model organisms at the single cell level are necessary to better dissect the role of specific genes and cell populations in development, disease, and therapy. Here, we describe a new optochemogenetic switch (OCG switch) to control CreER/loxP-mediated recombination via photoactivatable (″caged″) tamoxifen analogues in individual cells in cell culture, organoid culture, and <i>in vivo</i> in adult mice. This approach opens opportunities to more fully exploit existing CreER transgenic mouse strains to achieve more precise temporal- and location-specific regulation of genetic events and gene expression

Optochemogenetics (OCG) Allows More Precise Control of Genetic Engineering in Mice with CreER regulators

New approaches that allow precise spatiotemporal control of gene expression in model organisms at the single cell level are necessary to better dissect the role of specific genes and cell populations in development, disease, and therapy. Here, we describe a new optochemogenetic switch (OCG switch) to control CreER/loxP-mediated recombination via photoactivatable (″caged″) tamoxifen analogues in individual cells in cell culture, organoid culture, and <i>in vivo</i> in adult mice. This approach opens opportunities to more fully exploit existing CreER transgenic mouse strains to achieve more precise temporal- and location-specific regulation of genetic events and gene expression

Optochemogenetics (OCG) Allows More Precise Control of Genetic Engineering in Mice with CreER regulators

New approaches that allow precise spatiotemporal control of gene expression in model organisms at the single cell level are necessary to better dissect the role of specific genes and cell populations in development, disease, and therapy. Here, we describe a new optochemogenetic switch (OCG switch) to control CreER/loxP-mediated recombination via photoactivatable (″caged″) tamoxifen analogues in individual cells in cell culture, organoid culture, and <i>in vivo</i> in adult mice. This approach opens opportunities to more fully exploit existing CreER transgenic mouse strains to achieve more precise temporal- and location-specific regulation of genetic events and gene expression

Loss of <i>FoxO1</i> and <i>Smad3</i> results in the down-regulation of a common set of genes.

<p>Quantitative rtPCR was performed on mRNA isolated from adult <i>FoxO1</i> mutant (A) and <i>Smad3</i> mutant (B) incisors and compared to control littermates. Both mutants exhibited a similar trend in the down-regulation of genes known to be necessary for proper enamel development and maturation (*p<0.05, **p<0.01, ***p<0.001).</p