RESUMEN
Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
Asunto(s)
Marcha/genética , Caballos/genética , Caballos/fisiología , Mutación/genética , Médula Espinal/fisiología , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Codón sin Sentido/genética , Marcha/fisiología , Perfilación de la Expresión Génica , Frecuencia de los Genes , Caballos/clasificación , Islandia , Ratones , Datos de Secuencia Molecular , Vías Nerviosas/fisiología , Desempeño Psicomotor/fisiología , Médula Espinal/citología , Factores de Transcripción/deficiencia , Factores de Transcripción/metabolismoRESUMEN
Previous studies showed a positive effect of the DMRT3 "gait keeper" mutation on harness racing performance in Standardbreds, French-, and Nordic trotters. The mutation has also been shown to influence riding traits in multiple breeds. This study investigated the effect of the DMRT3 mutation on harness racing performance and riding traits in Finnhorses. Finnhorses used for harness racing (n = 180) and for riding (n = 59) were genotyped for the DMRT3 mutation. For the trotters the genotypes were evaluated for association with racing performance (number of starts, victories, placings, earnings, and race times). At 3-6 years of age the AA genotype was superior compared with the CA and CC genotypes. The AA horses had a significantly higher proportion of victories (P = 1.4×10(-6)) and placings (P = 4.1×10(-7)), better race times (P = 0.01), and earned more money (P = 0.009) compared with C-horses. For the Finnhorses used for riding the owners answered a questionnaire to score how well the horse performed the gaits walk, trot, and canter on a scale from 1 to 6. These scores were tested for association with the DMRT3 genotypes. Although AA horses were more successful as racehorses, the CC and CA horses appear more adapted for classical riding disciplines. The AA horses received significantly lower gait scores compared with C-horses for the majority of gaits. Except for rhythm in extended canter (P = 0.05), there were no significant differences between CA and CC horses. This study shows that there are different optimal genotypes for different disciplines and the DMRT3 mutation clearly influences gaits and performance in Finnhorses.