Investigating the Role of 1Q21.1 in Neurological Disease-Related Behaviors
Restricted (Penn State Only)
- Author:
- Thieu, Thanh Mai
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Yingwei Mao, Thesis Supervisor
Bernhard Luscher, Thesis Honors Advisor - Keywords:
- Autism Spectrum Disorder
ASD
Schizophrenia
SCZ
Neurodevelopmental Diseases
1q21.1
Copy Number Variant
Neuroscience
Behavioral Science - Abstract:
- The 1q21.1 locus has been of particular interest in the field of neurodevelopmental disease research because it spans across many genes, and mutations of this chromosomal region are tied to both ASD and SCZ as well as other, non-syndromic forms of developmental delay. More specifically, a 1q21.1 microduplication leads to increased risk for ASD, while a microdeletion in 1q21.1 leads to increased risk of SCZ. However, the cases investigated are few, and researchers are still trying to better understand the role of 1q21.1 in these diseases. This thesis investigated the role of 1q21.1 in behavior by using Df(h1q21.1)/+ mouse models. The Df(h1q21.1)/+ mice used are heterozygous for the microdeletion because the homozygous carriers were observed to die prematurely. The phenotypes related to 1q21.1 mutations are understudied, but they are hypothesized to result in behavior indicative of increased anxiety along with cognitive deficits and anti-social tendencies. To test this hypothesis, wild type and Df(h1q21.1)/+ heterozygous mice were subjected to a battery of behavioral tests (open field test, y-maze, social interaction test, forced swimming test, marble burying test, water spray-induced grooming behavior, as well as grip strength measurements) to examine possible alternations in affect, working memory, and social interactions as well as general physical fitness. Results from the forced swimming test indicate that these mice may have a tendency towards hyperactivity. Additionally, a decreased latency to enter the center shown by male Df(h1q21.1)/+ mice in the open field test indicated a paradoxical anxiolytic-like phenotype. The mutant mice behaved indistinguishably from the wild type mice in the Y-maze, marble burying test, grooming behavior, and grip strength measurements. This suggests that in mice, in the 1q21.1 microdeletion does not measurably affect working memory, obsessive-compulsive behaviors, and muscle function. The indistinguishable behavior among the wild type and mutant mice could be due to the way the cohorts of mice were generated and the age at which the mice were tested. In future studies, behavior tests measuring anxiety, cognitive and social deficits, and hyperlocomotion should be the primary focus, and the mice should be tested at 5-15 weeks of age. Further morphological analysis such as immunohistochemical staining is necessary to assess a possible connection between 1q21.1, behavior, and atypical brain pathology.