Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Publication

An Essential Postdevelopmental Role for Lis1 in Mice.

eNeuro | 2018

LIS1 mutations cause lissencephaly (LIS), a severe developmental brain malformation. Much less is known about its role in the mature nervous system. LIS1 regulates the microtubule motor cytoplasmic dynein 1 (dynein), and as LIS1 and dynein are both expressed in the adult nervous system, Lis1 could potentially regulate dynein-dependent processes such as axonal transport. We therefore knocked out Lis1 in adult mice using tamoxifen-induced, Cre-ER-mediated recombination. When an actin promoter was used to drive Cre-ER expression (Act-Cre-ER), heterozygous Lis1 knockout (KO) caused no obvious change in viability or behavior, despite evidence of widespread recombination by a Cre reporter three weeks after tamoxifen exposure. In contrast, homozygous Lis1 KO caused the rapid onset of neurological symptoms in both male and female mice. One tamoxifen-dosing regimen caused prominent recombination in the midbrain/hindbrain, PNS, and cardiac/skeletal muscle within a week; these mice developed severe symptoms in that time frame and were killed. A different tamoxifen regimen resulted in delayed recombination in midbrain/hindbrain, but not in other tissues, and also delayed the onset of symptoms. This indicates that Lis1 loss in the midbrain/hindbrain causes the severe phenotype. In support of this, brainstem regions known to house cardiorespiratory centers showed signs of axonal dysfunction in KO animals. Transport defects, neurofilament (NF) alterations, and varicosities were observed in axons in cultured DRG neurons from KO animals. Because no symptoms were observed when a cardiac specific Cre-ER promoter was used, we propose a vital role for Lis1 in autonomic neurons and implicate defective axonal transport in the KO phenotype.

Pubmed ID: 29404402 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

Antibodies used in this publication

Associated grants

Agency: NINDS NIH HHS, United States
Id: R01 NS041596
Agency: NINDS NIH HHS, United States
Id: R01 NS056314
Agency: NINDS NIH HHS, United States
Id: R01 NS089633
Agency: NIDA NIH HHS, United States
Id: R00 DA032681

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

BioLegend (tool)

RRID:SCR_001134

Commercial antibody supplier and developer for biomedical research. These products are compatible with use in flow cytometry and mass cytometry, immunoprecipitation and chip, western blotting, immunofluorescence microscopy, and quantitative multiplexing.

View all literature mentions

Novus Biologicals (tool)

RRID:SCR_004286

Commercial antibody vendor which supplies antibodies and other products to life science researchers.

View all literature mentions

Jackson Laboratory (tool)

RRID:SCR_004633

An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

View all literature mentions

Bio-Rad Laboratories (tool)

RRID:SCR_008426

Commercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.

View all literature mentions

AxioVision Imaging System (tool)

RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

View all literature mentions

FISHER (tool)

RRID:SCR_009181

THIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)

View all literature mentions

COMPASS (tool)

RRID:SCR_015874

Algorithm for MATLAB and the EEGLAB toolbox that enables the automatic detection of independent components from an ICA that represent event-related brain potentials. It performs automatic Independent Component (IC) selection with respect to the contributions of the ICs to a certain ERP.

View all literature mentions