KIAA1109 is required for survival and for normal development and function of the neuromuscular junction in mice

KIAA1109 (4932438A13Rik) is a novel gene linked to Alkuraya-Kucinska Syndrome, an autosomal recessive disorder with severe brain malformations and arthrogryposis in humans. The role of KIAA1109 in mammalian development and function remains poorly understood. Here, we characterize mutant mice deficient in Kiaa1109 (Kiaa1109-/-). We report that Kiaa1109-/- mice died during perinatal stages. These Kiaa1109-/- embryos exhibited impaired intramuscular nerve growth and reduced sizes of the neuromuscular junction (NMJ) compared with their littermate controls. Electrophysiological analysis further revealed defects in neuromuscular synaptic transmission in Kiaa1109-/- embryos. Notably, the frequency of spontaneous neurotransmitter release was markedly increased, whereas evoked neurotransmitter release and quantal content were reduced. Furthermore, neuromuscular synapses in Kiaa1109-/- embryos failed to respond to a repetitive, low frequency stimulation (10Hz). These results demonstrate that KIAA1109 is required for survival in mice and for proper development and function of the NMJ. Significance StatementThis is the first report characterizing the phenotype of mutant mice deficient in KIAA1109 (4932438A13Rik), a novel gene in mammals. We show that KIAA1109 is required for survival in mice and that KIAA1109 plays important roles in normal development and function of the NMJ in mice.