Functional, anatomical, and molecular determination of cardio-repertory deficiencies in neonate lethal mouse lines

Grantee: Baylor College of Medicine

The goal of this project is to characterize cardio-respiratory function in homozygous mutant mouse lines that die prior to weaning but are otherwise morphologically normal, a necessary step to define genes critical to cardio-respiratory pathophysiologies in infants and adults.

The estimated 1800 neonate homozygous mutants that die after birth but are otherwise anatomically normal offer a highly analogous resource for gene discovery in congenital pathophysiologies such as SIDS. To utilize this resource, additional phenotyping approaches are needed that can define lethal mechanisms in these mutants. This project presents a comprehensive pipeline to characterize cardio-respiratory function, carry out detailed anatomical analysis in brainstem respiratory circuits, and the profile brainstem gene expression signatures. This phenotyping pipeline will bridge physiological, anatomical, and molecular studies as a much needed step toward determining the underlying etiology of congenital pathophysiologies such as SIDS, Congenital Central Hypoventilation Syndrome, Rett Syndrome and others while creating a wealth of publicly available resources for additional studies.