Breeding Severely Vitamin B₁₂-Deficient Mice as Model Animals

Abstract

Newborn mice weaned from mice fed on a B12-deficient diet during pregnancy and lactation were fed on a B12-deficient diet for 90 days after weaning, and the state of B12 deficiency was evaluated. The effect of B12 deficiency on the testicular tissue was also examined. The body weight of the mice fed on a B12-deficient diet for 90 days was slightly lower than that of the control mice administrated CN-B12, and the urinary excretion of methylmalonic acid (MMA) was increased. The B12 concentrations in the liver and testes were markedly depressed by B12 deficiency, being about 13 and 10 pmol/g, respectively, on day 90. The testes weight was clearly reduced by B12 deficiency. The testes weight/100 g body weight was also lowered. Clear morphological changes were observed in the testicular tissue of the B12-deficient mice. These results showed that mice in a severely B12-deficient state could be produced by dietary B12 deprivation. These B12-deficient mice could be useful as model animals not only for elucidating the functions of B12 in vivo, but also for biochemical studies.

Testicular Injury to Rats Fed on Soybean Protein-Based Vitamin B12-Deficient Diet Can Be Reduced by Methionine Supplementation

“…Rats were fed the soybean protein-based B 12 -deficient diet for 120 d. We confirmed that those rats were in serious B 12 -deficiency by measuring urinary methylmalonic acid excretion and B 12 content in tissues. Methionine synthase activity in the testis of the B 12 -deficient rats was less than 2% of that in B 12 -supplemented (control) rats. To complement disrupted methionine biosynthesis, methionine was supplied in the diet.…”

“…A supplement of 5 g D,L-methionine per kg diet to the B 12 -deficient diet did not affect urinary methylmalonic acid excretion of B 12 -deficient rats. The testicular histology of rats fed the methioninesupplemented B 12 -deficient diet was almost indistinguishable from that of control rats. Thus, we conclude that the lowered testicular methionine synthase activity is the primary cause of the histologic damage due to B 12 -deficiency and that methionine supplementation to the diet can reduce the damage.…”

“…The testicular histology of rats fed the methioninesupplemented B 12 -deficient diet was almost indistinguishable from that of control rats. Thus, we conclude that the lowered testicular methionine synthase activity is the primary cause of the histologic damage due to B 12 -deficiency and that methionine supplementation to the diet can reduce the damage. These findings would indicate the importance of the methionine synthase activity, especially for testicular function.…”

“…In this paper, we report the effect of B 12 -deficiency on B 12 -dependent methionine synthase in the rats' testes and the effect of methionine supplementation of the diet on testicular damage. Rats were fed the soybean protein-based B 12 -deficient diet for 120 d. We confirmed that those rats were in serious B 12 -deficiency by measuring urinary methylmalonic acid excretion and B 12 content in tissues. Methionine synthase activity in the testis of the B 12 -deficient rats was less than 2% of that in B 12 -supplemented (control) rats.…”

“…There are two established animal models for study of the biochemical and nutritional functions of B 12 . One is the nitrous oxide (N 2 O, an anesthetic gas) exposed animal model ( 5 , 6 ).…”