Survival and growth of C57BL/6J mice lacking the BK channel, Kcnma1: lower adult body weight occurs together with higher body fat

Abstract

Big conductance potassium (BK) channels contribute to K ⁺ flow and electrical behavior in many cell types. Mice made null for the gene ( Kcnma1) producing the BK channel (BK ^KO) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0–P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20‐month period of building construction compared with the quiescent period after cessation of construction. Births during construction were not consistent with Mendelian predictions indicating the likelihood of a specific disadvantage induced by this environmental stressor. Later BK ^KO pup deaths (~P13) also were more numerous than Mendelian expectations. After weaning, weight gain was slower for BK ^KO mice compared with wild‐type littermates: 5 g less for male BK ^KO mice and 4 g less for female BK ^KO mice. Body composition determined by quantitative magnetic resonance indicated a higher fat proportion for wild‐type female mice compared with males, as well as a higher hydration ratio. Both male and female BK ^KO mice showed higher fat proportions than wild‐type, with female BK ^KO mice exhibiting greater variation. Together, these results indicate that BK ^KO mice suffered disadvantages that lead to prenatal and perinatal death. A metabolic difference likely related to glucose handling led to the smaller body size and distinct composition for BK ^KO mice, suggesting a diversion of energy supplies from growth to fat storage.