Disease model articles from across Nature Portfolio

Endocrine Disrupting Chemicals (EDCs) are a group of harmful environmental pollutants hypothesized to be drivers of multiple health disorders. In the current article, the estrogenic-EDC diethylstilbestrol (DES) is utilized to model how EDCs may impact erectile dysfunction, with DES causing abnormal erectile tissue contractility.

Disease-causing variants define a conserved and unique NR5A1 responsive enhancer for SRY expression to initiate testis-determination in humans. Modelling regulatory variants causing sex-reversal provides a tool to understand global enhancer activity.

Mutations in condensin subunits cause microcephaly, but the underlying molecular mechanisms remain elusive. Here, the authors show that unrestricted retrotransposable element activity impairs brain development in condensin insufficient organisms.

In mouse models of acute kidney injury, the outcome — scarless tissue repair versus fibrosis — depends on the activity of the transcription factor SOX9.

Pregestational diabetes is linked to an increased risk of congenital disorders, including cardiac and craniofacial defects, but the underlying mechanisms are unclear. Using a hyperglycemic mouse model, Nishino et al. show that ectopic retinoic acid signaling in the anterior heart field causes aberrant tissue patterning and associated pathologies¹.

BBLN, a protein with predominantly uncharted functions, serves as an instigator of CAMK2D autophosphorylation, leading to subsequent cardiac remodeling and failure in both humans and mice. The induction of BBLN is driven by hypoxia in TOF and/or pressure overload, as evidenced in mouse models.

Human-based in vitro models, such as organoids and organs-on-chips, may have the potential to replace certain animal models in preclinical research. But how much ‘human’ is needed in these models?

Several experimental systems have been used over the past five decades to address important questions in cardiac development and congenital heart disease. Here we discuss the strengths and limitations of available models, and how the use of different models synergistically is needed for a deeper understanding of these complex diseases.