Note
Includes bibliography.
Member of
Contributors
Publisher
Florida Atlantic University
Date Issued
2017
EDTF Date Created
2017
Description
Phosphatase and tensin homologue (PTEN) is a gene that, when mutated, can
cause macrocephaly/autism syndrome. The Pten mutant mouse model will help identify
genetic modifiers of Pten-related neurodevelopmental phenotypes, with the goal of
gaining insight into the polygenic nature of autism. We hypothesize that genes that
display spatiotemporal coexpression patterns similar to Pten in the developing brain are
candidates to genetically interact with Pten. Fbxw7, has been identified as a strong
candidate. We have conditionally deleted Fbxw7 (Fbxw7 cKO), Pten (Pten cHet), and
Pten and Fbxw7 together (Pten and Fbxw7 double mutant) in the developing cerebral
cortex. We found Fbxw7 cKO mice have decreased cortical mass and cell number,
increased cell density, hydrocephalus and premature lethality. Pten cHet mice display
increased cortical mass and cell number, with unchanged cell density and no
hydrocephalus or premature lethality. Strikingly, Pten and Fbxw7 double mutant mice
had the exact phenocopy of Pten cHet mice, indicating a surprising epistatic interaction
between Pten and Fbxw7, in which Pten overrides the effects of Fbxw7. Further work
will explore the mechanism of this interaction and will characterize cortical phenotypes
in mutant animals.
cause macrocephaly/autism syndrome. The Pten mutant mouse model will help identify
genetic modifiers of Pten-related neurodevelopmental phenotypes, with the goal of
gaining insight into the polygenic nature of autism. We hypothesize that genes that
display spatiotemporal coexpression patterns similar to Pten in the developing brain are
candidates to genetically interact with Pten. Fbxw7, has been identified as a strong
candidate. We have conditionally deleted Fbxw7 (Fbxw7 cKO), Pten (Pten cHet), and
Pten and Fbxw7 together (Pten and Fbxw7 double mutant) in the developing cerebral
cortex. We found Fbxw7 cKO mice have decreased cortical mass and cell number,
increased cell density, hydrocephalus and premature lethality. Pten cHet mice display
increased cortical mass and cell number, with unchanged cell density and no
hydrocephalus or premature lethality. Strikingly, Pten and Fbxw7 double mutant mice
had the exact phenocopy of Pten cHet mice, indicating a surprising epistatic interaction
between Pten and Fbxw7, in which Pten overrides the effects of Fbxw7. Further work
will explore the mechanism of this interaction and will characterize cortical phenotypes
in mutant animals.
Language
Type
Genre
Form
Extent
21 p.
Identifier
FA00012611
Additional Information
Includes bibliography.
Thesis (B.A.)--Florida Atlantic University, Harriet L. Wilkes Honors College, 2017.
FAU Honors Theses Digital Collection
Date Backup
2017
Date Created Backup
2017
Date Text
2017
Date Created (EDTF)
2017
Date Issued (EDTF)
2017
Extension
FAU
IID
FA00012611
Organizations
Attributed name: Florida Atlantic University
Attributed name: Harriet L. Wilkes Honors College
Person Preferred Name
Cabral, Stacy
author
Physical Description
application/pdf
21 p.
Title Plain
IDENTIFYING NOVEL GENETIC MODIFIERS OF BRAIN OVERGROWTH IN THE
CORTEX OF A MOUSE MODEL OF MACROCEPHALY/AUTISM SYNDROME
CORTEX OF A MOUSE MODEL OF MACROCEPHALY/AUTISM SYNDROME
Use and Reproduction
Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Origin Information
2017
2017
Florida Atlantic University
Jupiter, Florida
Physical Location
Florida Atlantic University Libraries
Place
Jupiter, Florida
Sub Location
Digital Library
Title
IDENTIFYING NOVEL GENETIC MODIFIERS OF BRAIN OVERGROWTH IN THE
CORTEX OF A MOUSE MODEL OF MACROCEPHALY/AUTISM SYNDROME
CORTEX OF A MOUSE MODEL OF MACROCEPHALY/AUTISM SYNDROME
Other Title Info
IDENTIFYING NOVEL GENETIC MODIFIERS OF BRAIN OVERGROWTH IN THE
CORTEX OF A MOUSE MODEL OF MACROCEPHALY/AUTISM SYNDROME