Phenotypes Associated with This Genotype

Genotype
MGI:7763621

• Allelic Composition: Kansl1^em1Cya/Kansl1^em1Cya; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: B6.Cg-Kansl1^em1Cya Tg(CAG-cre/Esr1*)5Amc

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cellular

abnormal neuron mitochondrial morphology ( J:327464 )

• primary neurons show an increase in the number of total mitochondria and damaged mitochondria

abnormal autophagy ( J:327464 )

• tamoxifen-treated murine embryonic fibroblasts (MEFs) show elevated ratio of LC3B-II to LC3B-1, indicating elevated autophagosome formation and accumulation after treatment with Earles Balanced Salt Solution (EBSS)

• tamoxifen-treated MEFs treated with EBSS and the autophagic inhibitor, bafilomycin A1, show unchanged ratio of LC3B-II/LC3B-I, suggesting no effect on induction of autophagic flux but more likely autophagosome degradation

• 13-cis retinoic acid can still rescue the autophagic defects when tamoxifen-treated primary neurons are treated with AGN 194310, a RAR pan-inhibitor

• however, docosahexaenoic acid, an agonist of RXR, does not rescue the autophagic defects in tamoxifen-treated primary neurons

abnormal mitophagy ( J:327464 )

• primary neurons treated with tamoxifen show an increase in the number of mitochondria in autophagosomes indicating that damaged mitochondria accumulate rather than undergo autophagic degradation

• primary neurons treated with tamoxifen and then 13-cis retinoic acid show restoration of the impaired mitophagic activity

oxidative stress ( J:327464 )

• tamoxifen-treated primary neurons show an increase in mitochondrial reactive oxygen species (ROS) levels

• primary neurons treated with tamoxifen and then 13-cis retinoic acid show a decrease in mitochondrial ROS accumulation

homeostasis/metabolism

abnormal autophagy ( J:327464 )

• tamoxifen-treated murine embryonic fibroblasts (MEFs) show elevated ratio of LC3B-II to LC3B-1, indicating elevated autophagosome formation and accumulation after treatment with Earles Balanced Salt Solution (EBSS)

• tamoxifen-treated MEFs treated with EBSS and the autophagic inhibitor, bafilomycin A1, show unchanged ratio of LC3B-II/LC3B-I, suggesting no effect on induction of autophagic flux but more likely autophagosome degradation

• 13-cis retinoic acid can still rescue the autophagic defects when tamoxifen-treated primary neurons are treated with AGN 194310, a RAR pan-inhibitor

• however, docosahexaenoic acid, an agonist of RXR, does not rescue the autophagic defects in tamoxifen-treated primary neurons

abnormal mitophagy ( J:327464 )

• primary neurons treated with tamoxifen show an increase in the number of mitochondria in autophagosomes indicating that damaged mitochondria accumulate rather than undergo autophagic degradation

• primary neurons treated with tamoxifen and then 13-cis retinoic acid show restoration of the impaired mitophagic activity

nervous system

abnormal neuron mitochondrial morphology ( J:327464 )

• primary neurons show an increase in the number of total mitochondria and damaged mitochondria

abnormal neuron physiology ( J:327464 )

• the autophagosome-lysosome fusion process in neurons is blocked in tamoxifen-treated primary neurons

• primary neurons treated with tamoxifen and then 13-cis retinoic acid show improvement of the decreased colocalization of autophagosomes and acid lysosomes, indicating partial rescue of the blocked autophagosome-lysosome fusion process in neurons

• hippocampal neurons exhibit lower oxygen consumption rates