Mice deficient in AKAP13 (BRX) develop compulsive-like behavior and increased body weight

Area of Science:

• Neuroscience
• Endocrinology
• Genetics

Background:

• Hormonal influences on obsessive-compulsive disorder (OCD) and obesity are known but poorly understood.
• A-kinase anchoring protein 13 (AKAP13) modulates estrogen receptor activity.
• AKAP13 is expressed in the hypothalamus and pituitary, regions involved in OCD and obesity.

Purpose of the Study:

• To investigate the role of AKAP13 in compulsive-like behaviors and body weight regulation.
• To utilize a haploinsufficient murine model (Akap13+/-) to study AKAP13 function.
• To determine if AKAP13 deficiency affects behavior and weight in a sex-dependent manner.

Main Methods:

• Generated Akap13 haploinsufficient mice.
• Assessed compulsive-like behaviors using marble-burying and grooming tests.
• Evaluated anxiety-like behaviors with open-field and elevated plus-maze tests.
• Measured brain and body weights.
• Analyzed data using multi-way ANOVA with genotype and sex as factors.

Main Results:

• Female Akap13 haploinsufficient mice exhibited significantly increased marble-burying and a trend towards increased grooming, indicating compulsive-like behaviors.
• Male Akap13 haploinsufficient mice showed no significant behavioral changes.
• No differences in brain weight were observed.
• Female Akap13 haploinsufficient mice showed a significant increase in body weight compared to wild-type females.
• No weight differences were found in male mice.

Conclusions:

• AKAP13 haploinsufficiency causes sex-dependent compulsive-like behaviors and increased body weight in mice.
• This study is the first to report AKAP13's involvement in murine behavior.
• Findings suggest AKAP13 plays a role in the pathophysiology of OCD, particularly in females, and may interact with sex hormones.