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The role of chromatin remodelling factors in cerebellar development and autism

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  1. Tez No: 402865
  2. Yazar: ÖMER KÜLHANCI
  3. Danışmanlar: DR. CATHY FERNANDES, DR. ALBERT BASSON
  4. Tez Türü: Yüksek Lisans
  5. Konular: Genetik, Genetics
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2015
  8. Dil: İngilizce
  9. Üniversite: University of London
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 61

Özet

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Özet (Çeviri)

Autism is a complex neurodevelopmental disorder with recognizable symptoms in early childhood, identified by three fundamental behavioural symptoms: persistent impairment social interaction, communication and restricted interest and repetitive behaviours. One percent of the population around the world is influenced by autism. Autism is associated with various rare genetic and medical conditions. CHARGE syndrome is one of the disorders under this umbrella term. Children with CHARGE syndrome and those with autism have overlapping behavioural traits, neuroanatomical defects, and genetic factors. One of the most implicated genes associated with CHARGE syndrome is CHD7 encoding the ATP-dependent chromatin remodeler. CHD7 gene is involved in development of cerebellum, which is consistently reported to be associated with neuroanatomical defects in individuals with autism. The mechanisms underlying deficits in the syndrome associated with the autistic features remain unidentified. Given the genomic, brain anatomy, pharmacological treatment response similarities between mice and human, animal models of psychiatric disorders emerged as tools to elucidate the exact role of genes and their effects over time by creating mutant phenotypes resembling human disease phenotypes. An investigation of the behavioural effects of the conditional Chd7 deletion in mice was performed to gain a better understanding of its role in ASD. Wildtype, knockout Chd7 male and female mice were tested for impairments in short-term memory (novel object discrimination task), spatial learning, reference memory and/or cognitive flexibility (Morris water maze task) (n = 12 per genotype, per sex). Alternative cognitive task for the assessment of short-term memory (spontaneous spatial novelty discrimination in a Y maze) was piloted in C57BL/6J mice to assess its utility for future behavioural work (n = 12, male). Cerebellar hypoplasia in Chd7 conditional knockout mice is associated with mild motor deficits. This study has several limitations that affect robustness in assessments of cognitive abilities in mice regarding few numbers of cognitive tests and evaluation of the mutant line. Although this work reports no strong behavioural deficiencies associated with cerebellar hypoplasia, these observations are still be of significant interest in elucidating isolated cerebellar hypoplasia because it is one of the main factors influencing autistic phenotypes associated with Chd7 deficiency.

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