Deletion of the Chd6 exon 12 affects motor coordination.
Members of the CHD protein family play key roles in gene regulation through ATP-dependent chromatin remodeling. This is facilitated by chromodomains that bind histone tails, and by the SWI2/SNF2-like ATPase/helicase domain that remodels chromatin by moving histones. Chd6 is ubiquitously expressed in both mouse and human, with the highest levels of expression in the brain. The Chd6 gene contains 37 exons, of which exons 12-19 encode the highly conserved ATPase domain. To determine the biological role of Chd6, we generated mouse lines with a deletion of exon 12. Chd6 without exon 12 is expressed at normal levels in mice, and Chd6 Exon 12 -/- mice are viable, fertile, and exhibit no obvious morphological or pathological phenotype. Chd6 Exon 12 -/- mice lack coordination as revealed by sensorimotor analysis. Further behavioral testing revealed that the coordination impairment was not due to muscle weakness or bradykinesia. Histological analysis of brain morphology revealed no differences between Chd6 Exon 12 -/- mice and wild-type (WT) controls. The location of CHD6 on human chromosome 20q12 is overlapped by the linkage map regions of several human ataxias, including autosomal recessive infantile cerebellar ataxia (SCAR6), a nonprogressive cerebrospinal ataxia. The genomic location, expression pattern, and ataxic phenotype of Chd6 Exon 12 -/- mice indicate that mutations within CHD6 may be responsible for one of these ataxias.
Lathrop
Melissa J
MJ
Department of Microbiology/Immunology, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03755, USA.
Chakrabarti
Lisa
L
Eng
Jeremiah
J
Rhodes
C Harker
CH
Lutz
Thomas
T
Nieto
Amelia
A
Liggitt
H Denny
HD
Warner
Sandra
S
Fields
Jennifer
J
Stöger
Reinhard
R
Fiering
Steven
S
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004265:DNA Helicases / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000235:genetics*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D004856:Postural Balance / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D004265:DNA Helicases; C550983:Chd6 protein, mouse