Tsc2 shapes olfactory bulb granule cell molecular and morphological characteristics

Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations that inactivate TSC1 or TSC2. Hamartin and tuberin are encoded by TSC1 and TSC2 which form a GTPase activating protein heteromer that inhibits the Rheb GTPase from activating a growth promoting protein kinase called mammalian target of rapamycin (mTOR). Growths and lesions occur in the ventricular-subventricular zone (V-SVZ), cortex, olfactory tract, and olfactory bulbs (OB) in TSC. Here, nestin­-CRE-ERT2 mice were injected with tamoxifen at postnatal days 2 and 3 and brains harvested at postnatal day 60. OBs were subsequently subjected to RNA sequencing. Overall design: nestin­-CRE-ERT2 mice were injected with tamoxifen at postnatal days 2 and 3 and brains harvested at postnatal day 60. OBs from three mice per condition were subsequently subjected to RNA sequencing.

结节性硬化症（Tuberous Sclerosis Complex, TSC）是一类由失活TSC1或TSC2的突变引发的神经发育障碍。TSC1与TSC2分别编码错构蛋白（hamartin）与结节蛋白（tuberin），二者可形成GTP酶激活蛋白异源多聚体，抑制Rheb GTP酶激活哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）——一种促进生长的蛋白激酶。TSC患者的脑室下区（ventricular-subventricular zone, V-SVZ）、皮层、嗅束及嗅球（olfactory bulbs, OB）中均可出现增生灶与病变。
本研究中，研究人员于出生后第2、3天对nestin-CRE-ERT2小鼠注射他莫昔芬，并于出生后第60天处死取材脑组织，随后对嗅球开展RNA测序（RNA sequencing）。
总体实验设计：于出生后第2、3天对nestin-CRE-ERT2小鼠注射他莫昔芬，并于出生后第60天收取脑组织；每组取3只小鼠的嗅球进行RNA测序。