Robo1 loss has pleiotropic effects on postnatal development and survival

Roundabout guidance receptor 1 (Robo1) is known to function during midbrain development in mice, but its postnatal role remains poorly defined in part due to the perinatal lethality of the mice lacking the gene. Here, we describe the postnatal phenotypes of Robo1-/- mice in the B6/129s genetic background. Robo1-/- mice had both a slower growth rate and shorter lifespan compared to Robo1+/+ littermates. Skin histological analysis revealed that Robo1-/- mice displayed increased wrinkles, enlarged sebaceous glands, and a reduced subcutaneous fat layer. Robo1-/- mice displayed accelerated hair graying in line with an observed overall decrease in melanin production. Although both growth hormone (GH) and insulin-like growth hormone 1 (IGF-1) were suppressed in Robo1-deficient mice at 3 weeks of age, they were expressed at similar levels to Robo1 intact mice at 7 weeks of age. These findings suggest that Robo1-mediated hormone regulation is required for normal growth during the early stages of puberty and may provide a crucial timepoint at which to examine the molecular mechanisms of pituitary disorders.