title: Assessment of ataxia phenotype in a new mouse model of galactose-1 phosphate uridylyltransferase (GALT) deficiency.
abstract: Despite adequate dietary management, patients with classic galactosemia continue to have increased risks of cognitive deficits, speech dyspraxia, primary ovarian insufficiency, and abnormal motor development. A recent evaluation of a new galactose-1 phosphate uridylyltransferase (GALT)-deficient mouse model revealed reduced fertility and growth restriction. These phenotypes resemble those seen in human patients. In this study, we further assess the fidelity of this new mouse model by examining the animals for the manifestation of a common neurological sequela in human patients: cerebellar ataxia. The balance, grip strength, and motor coordination of GALT-deficient and wild-type mice were tested using a modified rotarod. The results were compared to composite phenotype scoring tests, typically used to evaluate neurological and motor impairment. The data demonstrated abnormalities with varying severity in the GALT-deficient mice. Mice of different ages were used to reveal the progressive nature of motor impairment. The varying severity and age-dependent impairments seen in the animal model agree with reports on human patients. Finally, measurements of the cerebellar granular and molecular layers suggested that mutant mice experience cerebellar hypoplasia, which could have resulted from the down-regulation of the PI3K/Akt signaling pathway.
authors: Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.
authors: Wyman
authors: W
authors: Chen
authors: Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.|Dartmouth College, Hanover, NH, USA.
authors: Rose
authors: R
authors: Caston
authors: Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.
authors: Bijina
authors: B
authors: Balakrishnan
authors: Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Jacksonville, FL, USA.
authors: Anwer
authors: A
authors: Siddiqi
authors: Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Jacksonville, FL, USA.
authors: Kamalpreet
authors: K
authors: Parmar
authors: Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.
authors: Manshu
authors: M
authors: Tang
authors: Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.
authors: Merry
authors: M
authors: Feng
authors: Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT, 84108, USA. kent.lai@hsc.utah.edu.
authors: Kent
authors: 0000-0002-2377-9905
authors: K
authors: Lai
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005693:Galactosemias / Q000235:genetics*; D051379:Mice; D009043:Motor Activity / Q000235:genetics; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D006599:UDPglucose-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D006599:UDPglucose-Hexose-1-Phosphate Uridylyltransferase