title: Knockout of Lysosomal Enzyme-Targeting Gene Causes Abnormalities in Mouse Pup Isolation Calls.
abstract: Humans lacking a working copy of theGNPTABgene suffer from the metabolic disease Mucolipidosis type II (MLII). MLII symptoms include mental retardation, skeletal deformities and cartilage defects as well as a speech delay with most subjects unable to utter single words (Otomo et al., 2009; Cathey et al., 2010; Leroy et al., 2012). Here we asked whether mice lacking a copy of Gnptab gene exhibited vocal abnormities. We recorded ultrasonic vocalizations from 5 to 8 day old mice separated from their mother and littermates. AlthoughGnptab-/-pups emitted a similar number of calls, several features of the calls were different from their wild type littermates.Gnptab-/-mice showed a decrease in the length of calls, an increase in the intra-bout pause duration, significantly fewer pitch jumps with smaller mean size, and an increase in the number of isolated calls. In addition,Gnptab-/-mice vocalizations had less power, particularly in the higher frequencies.Gnptab+/-mouse vocalizations did not appear to be affected. We then attempted to classify these recordings using these features to determine the genotype of the animal. We were able to correctly identify 87% of the recordings as eitherGnptab-/-orGnptab+/+pup, significantly better than chance, demonstrating that genotype is a strong predictor of vocalization phenotype. These data show that deletion of genes in the lysosomal enzyme targeting pathway affect mouse pup isolation calls.
authors.affiliation: Department of Neuroscience, Washington University in St. Louis School of Medicine St. Louis, MO, USA.
authors.forename: Terra D
authors.initials: TD
authors.lastname: Barnes
authors.affiliation: Department of Neuroscience, Washington University in St. Louis School of Medicine St. Louis, MO, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Holy
keywords: Gnptab; lysosomal enzyme trafficking pathway; lysosomal enzymes; mouse ultrasonic vocalizations; mucolipidosis II