عنوان
پدید آورنده
موضوع
رده
کتابخانه
محل استقرار
NATIONAL BIBLIOGRAPHY NUMBER
Number
TL57969
LANGUAGE OF THE ITEM
.Language of Text, Soundtrack etc
انگلیسی
TITLE AND STATEMENT OF RESPONSIBILITY
Title Proper
Phenotypic Analysis of Motor Defects in Neuronal Ostm1 Conditional Loss of Function
General Material Designation
[Thesis]
First Statement of Responsibility
Hassan, Milhem Hajj
Subsequent Statement of Responsibility
Vacher, Jean
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
McGill University (Canada)
Date of Publication, Distribution, etc.
2020
GENERAL NOTES
Text of Note
100 p.
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
M.Sc.
Body granting the degree
McGill University (Canada)
Text preceding or following the note
2020
SUMMARY OR ABSTRACT
Text of Note
Mutations in the human and mouse Ostm1/Ostm1 gene result in the most severe form of autosomal recessive osteopetrosis, an inherited hematopoietic bone disorder. We isolated and characterized the Ostm1 gene responsible for the spontaneous murine osteopetrotic gl mutation and functional rescue of hematopoietic defects was obtained in PU.1-Ostm1 gl/gl BAC transgenic mice. However, these transgenic gl/gl mice became overtly ill and died prematurely around 6-7 weeks with severe neurodegeneration associated with impaired autophagy. To investigate whether Ostm1 has a direct role in neuronal cells, we generated a conditional Ostm1lox/lox allele to address the Ostm1 neuronal specificity with Synapsin1-Cre loss of function. Ostm1lox/lox SYN1-Cre+ progenies developed normally until ~7 weeks and were undistinguishable from control littermates. Around ~8-9 weeks of age Ostm1lox/lox Synapsin1-Cre+ mice developed a rapid and progressive neuronal deficit. These mice showed abnormal limb-clasping reflexes, severe motor defects and stopped gaining weight. Consistently, brain histology revealed inflammatory response with gliosis, loss of neuronal cells in CA3 and dentate gyrus of the hippocampus and thinning of the cortex. Spinal cord EM analysis showed axonal swelling with accumulation of vesicular structures similar to autophagosomes. End-stage disease is characterized by hind limbs paralysis consistent with reduced motor neurons population, neuromuscular junctions' pathology and muscle fiber atrophy. Together, our results provided evidence that the Ostm1 plays a major role in neuronal homeostasis and further establish an Ostm1 neuromuscular crosstalk.
UNCONTROLLED SUBJECT TERMS
Subject Term
Alzheimers disease
Subject Term
Apoptosis
Subject Term
Atrophy
Subject Term
Autophagy
Subject Term
Biology
Subject Term
Brain research
Subject Term
Cell division
Subject Term
Genetics
Subject Term
Genotype & phenotype
Subject Term
Mutation
Subject Term
Nervous system
Subject Term
Neurobiology
Subject Term
Neurodegeneration
Subject Term
Neurosciences
Subject Term
Physiology
Subject Term
Proteins
Subject Term
Rodents
Subject Term
Spinal cord
Subject Term
Transgenic animals
PERSONAL NAME - PRIMARY RESPONSIBILITY
Hassan, Milhem Hajj
PERSONAL NAME - SECONDARY RESPONSIBILITY
Vacher, Jean
CORPORATE BODY NAME - SECONDARY RESPONSIBILITY
McGill University (Canada)
ELECTRONIC LOCATION AND ACCESS
Electronic name
مطالعه متن کتاب p
[Thesis]
276903
a
Y
