The hypothalamus and pituitary gland are essential for regulating growth, homeostasis, fertility, water balance, and the stress response. These physiological processes are regulated by releasing hormones from the hypothalamus and hormones from the posterior and anterior lobes of the pituitary gland. People with congenital hypopituitarism (CH) have increased morbidity and mortality resulting from a loss of one or more pituitary hormones. CH can occur in isolation or as part of a syndrome with other midline defects, including holoprosencephaly and septo-optic dysplasia. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. 

Most mouse models of Combined Pituitary Hormone Deficiency (CPHD), the most common form of CH, have been excellent predictors of the human phenotype. As such, genetically engineered mice offer an important opportunity to improve our understanding of the genetic basis for CPHD and related disorders. The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. It is comprised of many phenotyping centers that have developed high throughput pipelines for characterizing, annotating, and disseminating the phenotypes associated with the null alleles for the targeted genes. One such center, Deciphering the Mechanisms of Developmental Disorders (DMDD), characterized the embryonic lethal and sub-viable phenotypes associated with 209 targeted genes generated in the UK. In their new study titled "Knockout mice with pituitary malformations help identify human cases of hypopituitarism", Dr. Shannon Davis and his colleagues used mouse embryonic imaging data generated by the DMDD project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations. Of the 209 knockout mouse lines, they identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis.