title: Comprehensive motor testing in Fmr1-KO mice exposes temporal defects in oromotor coordination.
abstract: Fragile X syndrome (FXS; MIM #300624), a well-recognized form of inherited human mental retardation is caused, in most cases, by a CGG trinucleotide repeat expansion in the 5'-untranslated region of FMR1, resulting in reduced expression of the fragile X mental retardation protein (FMRP). Clinical features include macroorchidism, anxiety, mental retardation, motor coordination, and speech articulation deficits. The Fmr1 knockout (Fmr1-KO) mouse, a mouse model for FXS, has been shown to replicate the macroorchidism, cognitive deficits, and neuroanatomical abnormalities found in human FXS. Here we asked whether Fmr1-KO mice also display appendicular and oromotor deficits comparable to the ataxia and dysarthric speech seen in FXS patients. We employed standard motor tests for balance and appendicular motor coordination, and used a novel long-term fluid-licking assay to investigate oromotor function in Fmr1-KO mice and their wild-type (WT) littermates. Fmr1-KO mice performed equally well as their WT littermates on standard motor tests, with the exception of a raised-beam task. However, Fmr1-KO mice had a significantly slower licking rhythm than their WT littermates. Deficits in rhythmic fluid-licking in Fmr1-KO mice have been linked to cerebellar pathologies. It is believed that balance and motor coordination deficits in FXS patients are caused by cerebellar neurophathologies. The neuronal bases of speech articulation deficits in FXS patients are currently unknown. It is yet to be established whether similar neuronal circuits control rhythmic fluid-licking pattern in mice and speech articulation movement in humans.
authors: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors: Snigdha
authors: S
authors: Roy
authors: Yu
authors: Y
authors: Zhao
authors: Melody
authors: M
authors: Allensworth
authors: Mohamed F
authors: MF
authors: Farook
authors: Mark S
authors: MS
authors: LeDoux
authors: Lawrence T
authors: LT
authors: Reiter
authors: Detlef H
authors: DH
authors: Heck
mesh_terms: D000818:Animals; D005152:Facial Muscles / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D009069:Movement Disorders / Q000235:genetics / Q000378:metabolism*; D004856:Postural Balance / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology*; D045442:Rotarod Performance Test / Q000379:methods; D013997:Time Factors
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse