Baz1b Dosage Influences Cardiovascular Function, Predisposing to Dilated Cardiomyopathy

Area of Science:

• Genetics
• Developmental Biology
• Cardiology

Background:

• BAZ1B (Williams Syndrome Transcription Factor) is implicated in neural crest cell migration and is deleted in Williams-Beuren Syndrome.
• Understanding BAZ1B's role is crucial given its association with a complex genetic disorder affecting development.

Purpose of the Study:

• To investigate the physiological consequences of BAZ1B loss-of-function using a mouse model.
• To determine the impact of BAZ1B dosage on survival, growth, and cardiac function.

Main Methods:

• Utilized a "knockout first" Baz1b mouse model (Baz1b^{tm2a(KOMP)Wtsi}) to assess gene expression and phenotype.
• Conducted survival analysis, weight monitoring, microCT, and echocardiography on mutant and wildtype mice.

Main Results:

• Baz1b mutant mice exhibited reduced gene expression, increased mortality (3x in heterozygotes, 16x in homozygotes), and significantly lower body weight compared to wildtypes.
• Echocardiography revealed mildly decreased ejection fraction and fractional shortening, with increased left ventricular internal dimension in heterozygous mutants, indicative of dilated cardiomyopathy.

Conclusions:

• BAZ1B dosage is critical for normal somatic growth and survival in mice.
• Loss of BAZ1B function leads to dilated cardiomyopathy and contributes to growth failure and early mortality.
• Further studies with conditional alleles are needed to elucidate mechanisms of growth and cardiac phenotypes.