Survival and Growth of C57BL/6J Mice Lacking the BK Channel (K Ca 1.1): Lower Adult Body Weight Occurs together with Higher Body Fat

The BK potassium channel contributes to K + flow and the electrical behavior of many cell types: including pancreatic β‐cells and cells in the hypothalamic‐pituitary‐adrenal axis. Mice made null for the gene ( Kcnma1, slo‐1 ) producing the BK channel exhibit numerous deficits in physiological functions, but also show resistance toward developing obesity on a high fat diet (Illison J, et al, Diabetes 2016 db160245). Initial breeding pairs lacking a single allele of Kcnma1 (BK het ) in a C57BL/6J background strain were obtained from Dr. Andrea Meredith at the University of Maryland. A colony derived by breeding these heterozygous mice had litter sizes of ~8 pups, 53% male. For the period of maternal care (P0 – P21) pup death peaked at P1 with a second less severe interval of pup death peaking near P13. The later deaths (~P13) of pups null for Kcnma1 (BK KO ) were greater than Mendelian expectations. Pup death at ~P1 was twice as likely during the 20 month construction of a building adjacent to the animal facility compared with the quiescent period after cessation of construction. Births also were not consistent with Mendelian predictions, indicating a specific prenatal disadvantage for female BK KO mice in the quiescent period and for female BK het mice during construction, a change likely induced by this environmental stressor. Death of colony mice after weaning was rare (~0.5%). After weaning, weight gain was lower for BK KO mice compared with wild‐type littermates: male BK KO mice were 5 g smaller and female BK KO mice were 4 g smaller. Lower weight gain for BK KO mice compared to wild‐type occurred in part due to an event of weight loss during the early post‐weaning period, between weeks 3 to 9. Interestingly, wild‐type mice as well as male BK KO mice were ~1 g larger during construction compared with mice during quiescence. Body composition determined by quantitative magnetic resonance (QMR) indicated a higher fat proportion for wild‐type female mice compared with males, as well as a higher hydration ratio (total water mass – free water mass/lean mass). Comparison of lean, fat, and water components for female and male mice suggested an interrelationship that governs changes to body composition. Both male and female BK KO mice showed higher fat proportions than wild‐type, with the female BK KO mice exhibiting a larger variation in fat content and male BK KO mice having a higher hydration ratio than wild‐type. Together these results indicate that BK KO mice suffered disadvantages that led to prenatal and perinatal death. A metabolic difference likely related to glucose handling led to the smaller body size and distinct composition with higher fat for BK KO mice, suggesting a diversion of energy supplies from growth to fat storage. Support or Funding Information [NIH DK65845; WSU‐BSoM Seed Grant]