Central pathology evaluation in a novel hypo catabolic mouse model of HD; R6/2; Ob/Ob mice
(2018) MOBN03 20172Degree Projects in Molecular Biology
- Abstract
- Huntington’s disease is a hereditary neurodegenerative disease caused by an expansion of CAG repeats in the huntingtin (HTT) gene. HD is fully penetrant around 40 CAG repeats and is characterized by motor impairments, psychiatric disturbances and cognitive deterioration. Unintended weight loss is also a clinical feature of HD, leading to reduced morality and a decline in quality of life in HD patients. Gathering data in the last few decades indicate that increased body weight and body mass index (BMI) may slow down disease progression. We based this study on the hypothesis that an increased body weight correlates with pathological features of HD. This hypothesis was tested by using a novel mouse model; R6/2; Ob/Ob, created by crossing the... (More)
- Huntington’s disease is a hereditary neurodegenerative disease caused by an expansion of CAG repeats in the huntingtin (HTT) gene. HD is fully penetrant around 40 CAG repeats and is characterized by motor impairments, psychiatric disturbances and cognitive deterioration. Unintended weight loss is also a clinical feature of HD, leading to reduced morality and a decline in quality of life in HD patients. Gathering data in the last few decades indicate that increased body weight and body mass index (BMI) may slow down disease progression. We based this study on the hypothesis that an increased body weight correlates with pathological features of HD. This hypothesis was tested by using a novel mouse model; R6/2; Ob/Ob, created by crossing the R6/2 mouse (HD) with Ob/Ob (obese) mouse to see whether higher BMI affected the onset of the disease. Central pathology and body weight of R6/2; Ob/Ob mice, and gene expression studies in the striatum and the prefrontal cortex were carried out, alongside analysis of inclusion number and size in the dorsal striatum. Furthermore, striatal volume, cortical and medial corpus callosum thickness were measured. Our results showed no changes in the central pathology between the novel R6/2; Ob/Ob mouse model and their R6/2 littermates. Body weight revealed that R6/2; Ob/Ob mice reached a plateau in body weight from 11-16 weeks but started to lose weight gradually as the disease progressed, indicating a hypermetabolic state in HD. Our central pathology results are inconclusive in regard to increased BMI and slower disease progression, we therefore intend to continue our analysis of the central pathology in R6/2; Ob/Ob mice, as lack of mice number might have affected our results. (Less)
- Popular Abstract
- Huntington’s disease (HD) is a rare genetic disorder that affects 1 in 7300 people in the western population. The inheritance pattern is an autosomal (autosome: non-sex chromosomes) dominant, meaning, if a person inherits one abnormal copy from a parent, the person will inherit the disease. The disease is caused by a faulty gene. This gene, under normal circumstances synthesise a protein called Huntingtin. However, because of the defect in the gene, it means that there is loss of normal huntingtin protein function in HD affected individuals, and instead there is synthesise of a toxic protein, called mutant huntingtin protein. Due to this loss of function of normal huntingtin protein and synthesis of the toxic mutant huntingtin protein,... (More)
- Huntington’s disease (HD) is a rare genetic disorder that affects 1 in 7300 people in the western population. The inheritance pattern is an autosomal (autosome: non-sex chromosomes) dominant, meaning, if a person inherits one abnormal copy from a parent, the person will inherit the disease. The disease is caused by a faulty gene. This gene, under normal circumstances synthesise a protein called Huntingtin. However, because of the defect in the gene, it means that there is loss of normal huntingtin protein function in HD affected individuals, and instead there is synthesise of a toxic protein, called mutant huntingtin protein. Due to this loss of function of normal huntingtin protein and synthesis of the toxic mutant huntingtin protein, severe clinical features affect individuals with this genetic disorder. While the exact mechanisms behind the disease are unknown, it is widely believed that the toxic proteins alter normal cellular functions and form toxic aggregates, causing neurons (brain cells) and peripheral tissues to degenerate. This in turn causes characteristics symptoms of HD, such as cognitive decline, involuntary movements called chorea, psychiatric changes and increased weight loss.
Previous studies have shown that there is a correlation between weight loss and Huntington’s disease. HD patients are believed to be characterised with higher energy expenditure, leading to increased weight loss. Recently it has been widely hypothesised the HD patients with increased body weight and body mass index (BMI [kg/m2] have a slower disease progression. In this study, we therefore aim to explore this hypothesis by comparing HD modelled mice (R6/2 mice) with a novel mouse model, called R6/2; Ob/Ob. This novel mouse model differs from the R6/2 model in the sense that the R6/2; Ob/Ob has HD but is obese and therefore has an increased BMI. We utilize this mouse model to further investigate whether increased BMI may slow down HD disease progression. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/8946981
- author
- Dandunna, Unali
- supervisor
- organization
- course
- MOBN03 20172
- year
- 2018
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 8946981
- date added to LUP
- 2018-06-08 13:22:47
- date last changed
- 2018-06-08 13:22:47
@misc{8946981,
abstract = {{Huntington’s disease is a hereditary neurodegenerative disease caused by an expansion of CAG repeats in the huntingtin (HTT) gene. HD is fully penetrant around 40 CAG repeats and is characterized by motor impairments, psychiatric disturbances and cognitive deterioration. Unintended weight loss is also a clinical feature of HD, leading to reduced morality and a decline in quality of life in HD patients. Gathering data in the last few decades indicate that increased body weight and body mass index (BMI) may slow down disease progression. We based this study on the hypothesis that an increased body weight correlates with pathological features of HD. This hypothesis was tested by using a novel mouse model; R6/2; Ob/Ob, created by crossing the R6/2 mouse (HD) with Ob/Ob (obese) mouse to see whether higher BMI affected the onset of the disease. Central pathology and body weight of R6/2; Ob/Ob mice, and gene expression studies in the striatum and the prefrontal cortex were carried out, alongside analysis of inclusion number and size in the dorsal striatum. Furthermore, striatal volume, cortical and medial corpus callosum thickness were measured. Our results showed no changes in the central pathology between the novel R6/2; Ob/Ob mouse model and their R6/2 littermates. Body weight revealed that R6/2; Ob/Ob mice reached a plateau in body weight from 11-16 weeks but started to lose weight gradually as the disease progressed, indicating a hypermetabolic state in HD. Our central pathology results are inconclusive in regard to increased BMI and slower disease progression, we therefore intend to continue our analysis of the central pathology in R6/2; Ob/Ob mice, as lack of mice number might have affected our results.}},
author = {{Dandunna, Unali}},
language = {{eng}},
note = {{Student Paper}},
title = {{Central pathology evaluation in a novel hypo catabolic mouse model of HD; R6/2; Ob/Ob mice}},
year = {{2018}},
}