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Circadian Clock Mutation in Dams Disrupts Nursing Behavior and Growth of Pups

Department of Physiology and Pharmacology, Waseda University School of Science and Engineering (K.H., Y.W., S.S.), Nishitokyo 202-0021, Japan; and Department of Applied Biochemistry, Faculty of Agriculture, Utsunomiya University (M.I.), Tochigi 321-8505, Japan

Address all correspondence and requests for reprints to: Dr. Shigenobu Shibata, Department of Physiology and Pharmacology, Waseda University School of Science and Engineering, Higashifushimi 2-7-5, Nishitokyo 202-0021, Japan. E-mail: shibatas{at}waseda.jp.

To understand the role of the circadian molecular clock in mouse reproduction, we investigated the daily rhythms associated with nursing and pup growth in Clock-mutant mice maintained under light-dark housing conditions. The daily rhythm associated with the maternal behavior of crouching had a strong diurnal peak and two weak nocturnal peaks in wild-type dams, whereas homozygotes (Clock/Clock) exhibited no significant peaks in activity. Wild-type, but not Clock-mutant, dams showed high, rhythmic levels of prolactin content in serum that corresponded with crouching. Pup body weight increased at a significantly slower rate in Clock-mutant dams compared with wild-type dams under all experimental conditions when the pups ranged from 10–15 in number. Heterozygote dams equally bred wild-type, heterozygote, or homozygote pups. The amount of milk secreted from dams, as calculated by the increase in pup body weight through suckling, was lower in Clock-mutant mothers vs. wild-type mice. When Clock-mutant dams gave birth to more than 10 pups, survival was poor for offspring until the time of weaning. The present results demonstrate that Clock mutation disrupts daily maternal behavior and the growth and survival rate of pups, especially with the breeding of more than 10 pups.

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