Conditional Smad7 Expression Alters Expression of Factors Important for Maintaining Adult β Cells

<div><p>Data are from tissues of male mice aged 4–5 mo.</p> <p>(A–C) Immunofluorescent detection of insulin⁺ β cells (green) and glucagon⁺ β cells (red) in wild-type, <i>Pdx1-tTA</i>, and bitransgenic <i>Pdx1-tTA/Smad7</i> mice. </p> <p>(C) Islet enlargement was detected in some bitransgenic <i>Pdx1-tTA/Smad7</i> mice following doxycycline withdrawal. </p> <p>(D) Islet morphology in paraffin sections appeared normal in bitransgenic <i>Pdx1-tTA/Smad7</i> animals 5 wk after readministration of doxycycline, as described in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040039#s4" target="_blank">Materials and Methods</a>. </p> <p>(E–H) Smad7 alters expression of MafA (red) in β cells expressing insulin (green).</p> <p>(F and G) The number of MafA-expressing β cells in bitransgenic <i>Pdx1-tTA/Smad7</i> was reduced compared to controls ( <i>n</i> = 3). </p> <p>(E and F) <i>Pdx1-tTA</i> animals also showed a mild decrease in numbers of MafA expressing islet cells relative to wild-type controls. </p> <p>(H) After diabetic bitransgenic <i>Pdx1-tTA/Smad7</i> animals were readministered doxycycline (+ <i>dox</i>), islet MafA expression appeared normal. Staining was performed on paraffin sections. </p> <p>(I–K, M–O) The expression of nuclear p27^kip1 (black, I–K) and Menin (red, M–O) was reduced in adult <i>Pdx1-tTA/Smad7</i> animals compared to wild-type and <i>Pdx1-tTA</i> controls ( <i>n</i> = 5). </p> <p>(L) After diabetic bitransgenic <i>Pdx1-tTA/Smad7</i> animals were readministered doxycycline (+ <i>dox</i>), p27^kip1 expression appeared relatively normal. </p> <p>(P–R) Nkx6.1 expression (red) was unchanged in <i>Pdx1-tTA/Smad7</i> animals. Arrows in (H) and (F) mark autofluorescent blood cells. Original magnification is 20× (A–D, I–L), and 63× (E–H, M–R). </p>