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Characterization of Adult Onset Lamin B1 Depletion in an Inducible Knockout Mouse Model

Munir, Anushe (2020) Characterization of Adult Onset Lamin B1 Depletion in an Inducible Knockout Mouse Model. Master's Thesis, University of Pittsburgh. (Unpublished)

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Autosomal dominant leukodystrophy (ADLD) is a rare, adult onset neurological disorder. It is a type of leukodystrophy that initially presents with autonomic dysfunction leading to cerebellar and pyramidal abnormalities as the disease progresses. ADLD is caused by an overexpression of LMNB1 located on chromosome 5q23.2. Currently numerous potential therapies are being investigated where the aim is to reduce this gene’s overexpression in an attempt to manage the symptoms. However, previous research carried out using knockout mouse models has established Lmnb1 as a critical component essential during development. Studies focusing on total Lmnb1 knockout mice recorded postnatal lethality due to multiple pathologies impacting organ development and severe abnormalities in skeletal structure. The public health significance of our study lies in how we aim to explore the effects of Lmnb1 reduction in adulthood as a precursor to developing effective therapies for ADLD. We demonstrate how the ablation of Lmnb1 in adult mice impacts their phenotype; behavior and overall molecular makeup, in an attempt to observe any deleterious effects that may arise. Using a tamoxifen inducible Cre/LoxP system, we created conditional knockout mice where the Lmnb1 gene was targeted for deletion only in adulthood. After collecting, quantifying and studying our behavioral, molecular, and immunofluorescence data we were able to demonstrate that reduced Lmnb1 expression in adulthood produced no obvious pathological alterations.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Munir, AnusheANM315@pitt.eduANM315
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairPaidath, Quasar
Committee MemberNicholls, Robert
Committee MemberUrban,
Date: 30 July 2020
Date Type: Publication
Defense Date: 11 June 2020
Approval Date: 30 July 2020
Submission Date: 2 July 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 42
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Autosomal Dominant Leukodystrophy Mouse Model Conditional Knockout Mice Genetics Over expression
Date Deposited: 31 Jul 2020 02:36
Last Modified: 31 Jul 2020 02:36


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