High‐throughout Screening of Circadian Rest/Activity Cycle Can Detect Significant Differences Estimates of Sleep/Wake Cycle In ENU Knockout Inbred Strains Of Rats

Abstract

17 ENU‐mutant rat strains of both genders were screened via a new high throughput system for circadian rest/activity behavior. The ENU targeted genes were selected for their involvement in cardiovascular disease models. The screening system consisted of 12 plethysmographic chambers with movement acquired by horizontal and vertical sensors while the rats were exposed to 3 – 12 hr light:dark cycles (0800:2000 hrs). Based on previous analysis, movement during the last 24 hours in 5 strains (both genders; FHHMCW, FHH‐Lcat, FHH‐Slc8a2, FHH‐Ghsr, FHH‐Agtr1b) were analyzed for Awake (Aw), Quiet (Qt), Sleep (Sp) and Sustained Sleep (SS) periods and summarized per hour. All strains of both genders showed significant* circadian variation in Aw, Sp and SS except for Sp in FHH‐Slc8a2 males. FHH‐Slc8a2 males showed significant* decreases in SS (15–20%) during the light cycle and increases (9–13%) during dark cycle with significant* reciprocal changes in Aw compared to FHH males. These data show that high throughput screening can discriminate between different estimates of circadian sleep/wake cycle in ENU‐mutant rat strains. Furthermore, these data show that ENU targeted genes selected for one disease model may have effects on multiple systems that can be used for further genetic dissection of complex traits in rodent models susceptible to cardiovascular and sleep dysfunction. Study funded by NHLBI (U01 HL66579) (*P < 0.05)