Laboratory Animal Science

| A spontaneous neurological mutation was detected in a colony of Sprague Dawley rats. The animals developed a progressive neurological syndrome characterized by tremor (which appeared at the age of 1 month), ataxia (at 4 months), immobility episodes (after 5-6 months), audiogenic seizures and hindlimb paralysis (after 10 months). Cross breeding experiments indicate that this is an autosomal recessive mutation, which we have named taiep subline. Genetically determined abnormalities of the central and peripheral nervous systems occur in several animal species. Among laboratory animals, the majority of these disorders have been described in mice (1,2) and only very few in rats (3-9). In this report a new spontaneous mutation in Sprague Dawley rats is described, characterized by tremor, ataxia, tonic immobility episodes, audiogenic seizures and progressive hindlimb paralysis. We have named this mutation taiep, by coining a word with the first letter of its principal symptoms: tremor, ataxia, immobility, epilepsy and paralysis. Materials and Methods In generation F4 of a selective inbreeding procedure of Sprague Dawley rats, originally obtained in 1981 from the Animal House of the Centro Médico Nacional del Instituto Mexicano del Seguro Social, Mexico, a few animals from one litter exhibited a fine tremor of the tail and the proximal part of the hindlimbs at 1 month of age. By inbreeding of these animals the taiep subline was obtained. The animals were maintained under standard conditions, housed in plastic cages on wood shavings, in a 12-12 light-dark cycled room (dark onset at 1900 hours). Food (Purina Chow) and water were freely available. Since adult mutant rats older than 6 months have difficulties eating from the upper wire mesh basket, food pellets and fresh carrots were offered to them on the floor of the cages. Because their motor disabilities also affect grooming and washing behavior, the adult mutants were bathed in tepid 0.1% aqueous solution of Neguvon (Bayer) once a month. Cross matings were with 2-3 months old rats. A From the Departamento de Ciencias Fisiológicas, Instituto de Ciencias, Universidad Autónoma de Puebla, Puebla, Mexico. week before parturition females were housed alone. Pups were weaned when 30 days old. No neurological signs or physical characteristics allow identification of the mutants before the appearance of tremor, which was quite evident at 30-40 days of age. All animals were observed systematically until they were 2 months old, in order to be certain that the syndrome did not appear later. Tremor was recorded using the technique described by Shinozaki (9), which measures the electromotive force induced on a wire coil, by the movements of a small magnet attached with adhesive tape to the skin of the sacral region of the animal. The coil was located below the platform on which the animal was placed, inside a glass cylinder (diameter 190 mm, height 100 mm). The electromotive force induced by movement (tremor) was amplified and filtered to attenuate components above 30 Hz. The resultant signal was sampled using an A/D converter (Tecmar Lab MasterTM), connected to an IBM PC® compatible microcomputer. The program for data acquisition and analysis was written in Turbo PascalTM. Data samples (5120) were acquired at 1/60 second intervals. The digital record was stored in a floppy disk for off-line analysis using a fast Fourier transform algorithm as an estimator of the power spectrum. In order to enhance the tremor components in relation with random movements, power spectra were estimated averaging ten contiguous blocks of 512 data points. Susceptibility to audiogenic seizures was tested by placing the animals in a cylindrical metal chamber (diameter: 55 cm, height: 26 cm). A loud buzzer (103 dB) was located on the upper part of the inside surface of the chamber. After a short period of adaptation (1 minute), the sound stimulus was suddenly and continuously applied for a standard period of 30 seconds. When tonicclonic convulsive seizures appeared, the sound was turned