Cerebellar defects in Pdss2 conditional knockout mice during embryonic development and in adulthood

Area of Science:

• Developmental Biology
• Neuroscience
• Genetics

Background:

• PDSS2 gene mutations cause primary ubiquinone deficiency, impacting human health.
• Ubiquinone deficiency frequently affects the cerebellum, leading to cerebellar atrophy in infants.
• Conditional knockout mouse models are crucial for studying gene function in specific tissues and developmental stages.

Purpose of the Study:

• To investigate the role of PDSS2 in cerebellum development and function using conditional knockout mouse models.
• To elucidate the cellular and molecular mechanisms underlying cerebellum hypoplasia in early development.
• To establish mouse models for studying ubiquinone deficiency in both embryonic and adult stages.

Main Methods:

• Generation of two Pdss2 conditional knockout mouse lines (Pax2-cre and Pcp2-cre).
• Analysis of cerebellum development, cell proliferation, migration, and apoptosis.
• Electron microscopy to examine mitochondrial structure and cellular pathology.
• Assessment of neurological symptoms and survival rates in knockout mice.

Main Results:

• Pdss2 knockout in Pax2-cre mice caused severe cerebellum hypoplasia, delayed neurodevelopment, and early lethality.
• Mitochondrial defects and autophagic vacuolization were observed in the developing cerebellum.
• Pdss2 knockout in Pcp2-cre mice led to Purkinje cell loss and ataxia in adulthood.
• The Pax2-cre model recapitulated infant ubiquinone deficiency symptoms, while the Pcp2-cre model serves as an adult disease model.

Conclusions:

• PDSS2 is essential for normal cerebellum development, with its deficiency impairing cell migration and proliferation.
• Conditional knockout of PDSS2 in mice provides valuable models for studying ubiquinone deficiency-related neurological disorders.
• These models will aid in understanding disease pathogenesis and developing therapeutic strategies for ubiquinone deficiency.