Mice deprived of pantothenic acid develop a movement disorder and azoospermia

Abstract

We asked whether a movement disorder could be elicited by deprivation of pantothenic acid (PA), the substrate for pantothenate kinase 2 (Pank2) since Pank2 null mice failed to show the neurological manifestations of the human disease, pantothenate kinase associated neurodegeneration. Wild type and Pank2 mice on PA diets (0 mg/kg) both fare poorly. PA-deficient animals have ungroomed fur with gray patches, decreased body weight, and a movement disorder developing around 20 weeks. Wild type mice on PA-deficient diets develop a movement disorder with their belly low because of a low-lying pelvis and slow steps. Rear limbs seem to drag and are occasionally extended into unnatural postures for 16–17 sec duration, possibly indicative of dystonia. Although most PA-deficient Pank2 mice die precipitously before we can discern a neurological problem, we have observed a few who exhibit neurological symptoms similar to those of the wild-type animals prior to death. Wild-type mice on PA deficient diets also become azoospermic, reminiscent of the Pank2 mice. PA supplementation of PA-deficient mice yields improvement in general health and grooming, weight gain, reversal of the movement disorder, and restoration of mature sperm within 4 weeks. We also tested 2 and 5 mg/kg PA in an attempt to elicit a less severe phenotype seen in PA-deficient Pank2 mice. Behavior of mice on 5 mg/kg diets is similar to those on control diets. On 2 mg/kg diets, wild type and mutant mice have weight loss, graying of fur and poor grooming but no movement disorder, even after 1 year of diet. Supported by an NIH grant (SJH) and HHMI (JG).