Mice deficient in APOBEC2 and APOBEC3.

Area of Science:

• Biochemistry
• Genetics
• Immunology

Background:

• The activation-induced deaminase/apolipoprotein B-editing catalytic subunit 1 (AID/APOBEC) family includes DNA and RNA-modifying enzymes.
• While AID is crucial for antibody diversification and some APOBEC3s restrict viral replication, the functions of APOBEC2 and mouse APOBEC3 remain largely unknown.
• APOBEC3s are hypothesized to protect against endogenous retroelements, and APOBEC2 is muscle-specific with no known deaminating activity.

Purpose of the Study:

• To investigate the in vivo functions of mouse APOBEC2 and mouse APOBEC3.
• To determine if these AID/APOBEC family members are essential for mouse development, survival, and fertility.

Main Methods:

• Gene targeting to create knockout mouse models for APOBEC2 and APOBEC3.
• Phenotypic analysis of knockout mice, including assessment of development, survival, and fertility.
• Biochemical assays to assess deaminating activity of APOBEC2.

Main Results:

• Mouse APOBEC2, despite being an ancestral member, is dispensable for mouse development, survival, and fertility.
• Mouse APOBEC3, despite being a DNA deaminase and proposed to restrict retrotransposition, is also inessential for mouse development, survival, and fertility.
• No evidence of cytidine deaminating activity was found for mouse APOBEC2 on free nucleotides or DNA.

Conclusions:

• Mouse APOBEC2 and APOBEC3 are not essential for the overall fitness of the organism.
• The proposed roles of APOBEC3 in endogenous retroelement restriction and APOBEC2 in muscle function may not be critical in vivo.
• Further research is needed to elucidate the precise biological roles, if any, of these specific mouse AID/APOBEC family members.