Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Analysis of lissencephaly-causing LIS1 mutations.

T Sapir1, M Eisenstein, H A Burgess

  • 1Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.

European Journal of Biochemistry
|December 3, 1999
PubMed
Summary

Mutations in the LIS1 gene cause lissencephaly by affecting brain development. Our study shows that LIS1 gene mutations, including point mutations and deletions, reduce correctly folded LIS1 protein, impacting brain structure.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Gsx1 expression defines neurons required for prepulse inhibition.

Molecular psychiatry·2014
Same author

A new process-centered description tool to initiate meta-reporting methodology in healthcare - 7CARECAT™. Feasibility study in a post-anesthesia care unit.

Annales francaises d'anesthesie et de reanimation·2013
Same author

Unidirectional startle responses and disrupted left-right co-ordination of motor behaviors in robo3 mutant zebrafish.

Genes, brain, and behavior·2009
Same author

Development of a 25-plex SNP assay for traceability in cattle.

Animal genetics·2009
Same author

[Neurobiology of the chronicisation of pain in children: the memory of pain and its painful memory].

Annales francaises d'anesthesie et de reanimation·2007
Same author

[Novelties in interventional pain techniques].

Revue medicale suisse·2006

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Mutations in the LIS1 gene are linked to lissencephaly, a severe brain malformation characterized by abnormal cortical development.
  • The primary mechanism for LIS1-related lissencephaly is often haploinsufficiency due to large deletions of the LIS1 gene.

Purpose of the Study:

  • To investigate the structural and functional consequences of various LIS1 gene mutations.
  • To determine how point mutations, deletions, and truncations affect LIS1 protein folding and stability.

Main Methods:

  • Introduction of specific point mutations and truncations into the LIS1 protein.
  • Analysis of protein folding using gel filtration and sucrose density gradient centrifugation.
  • Assessment of protein stability through resistance to trypsin cleavage.

Related Experiment Videos

Main Results:

  • Studied the effects of a point mutation (H149R), an internal deletion (Delta301-334), and a truncation mutation.
  • Introduced additional point mutations and truncations to probe LIS1 structure-function relationships.
  • Observed that all investigated LIS1 mutations, including point mutations, internal deletions, and truncations, lead to reduced levels of correctly folded LIS1 protein.

Conclusions:

  • LIS1 mutations associated with lissencephaly, including point mutations, internal deletions, and truncations, destabilize the protein.
  • These mutations result in a significant reduction in the amount of properly folded LIS1 protein, underlying the observed brain abnormalities.