Autosomal recessive myotonia congenita in sheep

La myotonie congenitale chez le mouton cause des episodes de raideur musculaire suite a divers stimuli. Ces episodes sont passagers et ne sont pas nuisibles a l'animal. Elle concernait trois agneaux mâles et trois agneaux femelles dans le troupeau d'origine. Deux des animaux affectes resultaient de l'accouplement d'un belier non affecte avec les filles non affectees d'un second belier non affecte. Cet accouplement a produit 25 animaux normaux en plus des animaux myotoniques, ce qui est coherent avec l'hypothese d'un gene autosomal recessif responsable du syndrome, en supposant que le pere et le grand-pere maternel etaient les seuls ancetres portant le gene (X 2 = 0,64, 1 df, p > 0,25). Les quatre autres animaux affectes avaient ces deux beliers dans leurs pedigrees, tant du cote paternel que du cote maternel, ce qui suggere que ces deux beliers pourraient avoir introduit le gene dans le troupeau.


INTRODUCTION
Myotonia congenita is a condition of skeletal muscles, which is characterized by rigid contraction of the muscles, generally following a startling stimulus. Myotonia congenita has been described in humans, goats and other species (Bryant, 1979;Ptacek et al, 1993). Myotonia congenita is distinct from hyperkalemic periodic paralysis, paramyotonia, as well as from myotonic dystrophy. Myotonia congenita in humans has two major forms. One is due to an autosomal dominant gene and the other is due to an autosomal recessive gene (Ptacek et al, 1993).
Myotonic animals are consistently heavily muscled, and this development of muscle is related to the myotonia. The heavy muscling of myotonic animals may offer some advantages to meat production systems. Myotonic sheep occurred in a single flock, and flock records were studied to determine the mode of inheritance within this flock.

MATERIALS AND METHODS
Myotonia congenita in sheep was detected in a flock that was used for the production of show lambs. Two affected sheep from the flock were evaluated by routine blood and urine analyses. These two sheep were also evaluated by electromyography. Samples from the biceps femoris muscle were evaluated histologically following routine processing for hematoxylin-and eosin-stained tissue sections. Flock records of pedigrees, production data, and evaluation of lambs as affected and unaffected, were evaluated for evidence of mode of genetic transmission of the myotonia congenita.

RESULTS
Clinical investigation of two affected animals from the flock revealed normal complete blood counts, normal biochemical profiles, and normal levels of creatine kinase. Urine analysis was also normal. The only histological change was hypertrophy of both type I and type II myofibers in the biceps femoris muscles.
Several muscles of each lamb were investigated electromyographically, and all of these exhibited classic myotonic potentials (Kimura, 1983). The myotonic discharges occurred as sustained runs of positive or negative waves up to 1 mV. These ranged about 50-100 impulses per second, which produced a diminishing buzz over the speaker of the electromyograph. This diminishing buzz is characteristic of myotonia congenita. Evaluation of herd records revealed that myotonia congenita was only expressed in lambs descended from two specific rams that were themselves unaffected, and not from two other unaffected rams that were also used in the flock. The two rams capable of producing affected lambs produced six affected lambs, three ram lambs and three ewe lambs. Two of the affected lambs resulted from the mating of one specific ram to the unaffected daughters of the other ram, this specific combination also producing 25 unaffected lambs. The other four affected lambs were the progeny of animals that were offspring or paternal grandoffspring of one of the rams, and maternal grandoffspring of the other. No affected lambs were produced from any mating that did not have at least one of these rams in both the maternal and paternal portion of the pedigree. These two rams were both brought into the flock from other sources, neither was born into the flock.

DISCUSSION
The clinical investigation was consistent with this disease being myotonia congenita. The electromyography was consistent with this, and the hypertrophy of the skeletal muscles was consistent with myotonia congenita and not with dystrophic diseases characterized by myotonia.
If an allele is recessive and is newly introduced into a population by an heterozygous male, then the mating of this heterozygous male to daughters of an heterozygous male (himself or another) should produce a 1:7 ratio, which fits the production of 25 unaffected and two affected lambs by one ram from daughters of another (x 2 = 0.64, 1 df, p > 0.25). This logic is correct only if the original flock lacked animals heterozygous for this gene, in which case the original frequency of the gene is zero. The pedigree information behing the four myotonic lambs that were not produced by the specific sire x maternal grandsire matings are consistent with the gene being introduced by the two rams and not existing in the flock before their use.
The only instances of affected lambs in this flock followed matings in which these two rams appeared in both the maternal and paternal pedigrees. In no other instance were affected lambs produced, which is evidence against this gene existing in the flock before these two rams were introduced. The overall production of three ram and three ewe lambs affected with myotonia congenita further indicates a lack of sex linkage for the gene responsible for this trait in sheep. The name Myotonia congenita is suggested for the locus of this allele, with the symbol Mc. The allele name myotonic is suggested for the recessive allele, with the symbol Mc7&dquo;!. This allele was unfortunately not documented prior to the publication of Mendelian Inheritance in Sheep (MIS 196) (Lauvergne et al, 1996), and the authors suggest that it be included in the next catalogue with the proposed names and symbols.
Myotonia congenita in sheep is similar to that in goats (Bryant, 1979) and humans (Ptaced et al, 1993). Clinical signs in the lambs were first noted at a few weeks to a few months of age. The first clinical sign was that the affected lambs had dirty fleeces. This is unusual in normal sheep since they rarely if ever recline laterally or roll, which generally keeps fleeces clean and free of soil. The affected lambs were then observed to exhibit extensor rigidity in the face of various stimuli, as is common with myotonia congenita in other species. This rigidity can occasionally cause them to fall over, and this accounts for the dirty fleeces as the lambs begin to express the trait.
The affected lambs were subjectively considered by the flock owner to have heavier muscling than the unaffected lambs. Further study of this aspect of myotonia congenita was not studied since only affected lambs were donated for evaluation. If further studies indicate that myotonic lambs are more heavily muscled than nonmyotonic lambs, then this allele might have applications in meat producing systems. Another recently documented gene with large effect on muscling is the callipyge gene (Jackson and Green, 1993), which unfortunately also results in toughness of some portions of the carcass. The non-expression of the callipyge allele in animals inheriting it from the dam also may limit its usefulness in production systems (Cockett et al, 1996).