Date of Award


Degree Name

Doctor of Philosophy




Anita M. Quintana


Methylmalonic aciduria and homocystinuria, CblC type (cblC) syndrome (MIM 277400) is a genetic disorder resulting from a mutation in the MMACHC gene. This gene plays a crucial role as a chaperone in the conversion of vitamin B12 into its active form, which is essential for proper cellular metabolism. cblC syndrome is heterogenous by nature, primarily attributed to the extensive damage it causes across multiple bodily systems. In cases of early onset of cblC syndrome, patients may exhibit a diverse range of clinical symptoms including difficulties with feeding, dysmorphic features, microcephaly, brain abnormalities, hypotonia, developmental delays, and seizures. The study of the disease manifestation is rendered impossible in the murine model due to its embryonic lethality. In this study, we aim to describe a behavioral and facial dysmorphic phenotype observed in a viable mmachc mutant zebrafish model of cblC. We have discovered that mmachc is linked to atypical behavior, which provides valuable insights into studying the early stages of brain development. Furthermore, our research has revealed the emergence of craniofacial malformations resulting from the mutation of mmachc. Thus, our study represents a pioneering effort to examine the behavioral phenotypes resulting from mutations in mmachc. In addition, we reveal a significant role for mmachc in craniofacial development, which is distinct from its involvement in vitamin B12 metabolism. The results obtained collectively provide valuable insights into the craniofacial and behavioral phenotypes, which contribute significantly to our ongoing efforts in comprehending the functional significance of MMACHC.




Recieved from ProQuest

File Size

85 p.

File Format


Rights Holder

Briana Elise Pinales