GSH-4 ENCODES A LIM-TYPE HOMEODOMAIN, IS EXPRESSED IN THE DEVELOPING CENTRAL-NERVOUS-SYSTEM AND IS REQUIRED FOR EARLY POSTNATAL SURVIVAL

We present an initial characterization of the murine Gsh-4 gene which is shown to encode a LIM-type homeodomain. Genes in this category are known to control late developmental cell-type specification events in simpler organisms. Whole mount and serial section in situ hybridizatio ns show transient Gsh-4 expression in ventrolateral regions of the dev eloping neural tube and hindbrain. Mice homozygous for a targeted muta tion in Gsh-4 suffer early postnatal death resulting from immature lun gs which do not inflate. Prenatal administration of progesterone and g lucocorticoid, to extend gestational term and accelerate maturation, r esulted in lung inflation at birth. Nevertheless, the hormonally treat ed mutants generally failed to survive beyond an hour after birth, due to ineffective breathing efforts. It is concluded that Gsh-4 plays a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung.