Probing the relationship between BTBD9 and MEIS1 in C. elegans and mouse

Abstract

Restless legs syndrome (RLS) is a neurological disorder characterized by an urge to move and uncomfortable sensations. Genetic studies have identified polymorphisms in up to 19 risk loci, including MEIS1 and BTBD9. Rodents deficient in either homolog show RLS-like phenotypes. However, whether MEIS1 and BTBD9 interact in vivo is unclear. Here, with C. elegans, we observed that the hyperactive egg-laying behavior caused by loss of BTBD9 homolog was counteracted by knockdown of MEIS1 homolog. This was further investigated in mutant mice with Btbd9, Meis1, or both knocked out. The double knockout mice showed an earlier onset of the motor deficit in a wheel running test but did not have increased sensitivity to heat stimuli as observed in single knock outs. Meis1 protein level was not influenced by Btbd9 deficiency, and Btbd9 transcription was not affected by Meis1 haploinsufficiency. Our results demonstrate that MEIS1 and BTBD9 do not regulate each other.

Deficiency of Meis1, a transcriptional regulator, in mice and worms: Neurochemical and behavioral characterizations with implications in the restless legs syndrome

“…Interestingly, mice knocked out of Btbd9 , the other gene associated with RLS (Schormair et al., 2017; Winkelmann et al., 2007), have decreased striatal D2R (Lyu, Doroodchi, Xing, et al, 2020). Our earlier studies show Btbd9 and Meis1 do not interact in both worm and mice (Lyu, Doroodchi, Sheng, et al, 2020). Hence, knockouts of Meis1 and Btbd9 may lead to RLS by distinctive pathophysiology.…”

“…Using a standard feeding method with HT115 bacterial strain (Kamath, Martinez‐Campos, Zipperlen, Fraser, & Ahringer, 2001), we seeded the plates with RNAi against unc‐62 ( unc‐62 RNAi or unc‐62 ) (Kamath et al., 2003), or the EV. The number of eggs retained in utero was measured as before (Chase & Koelle, 2004; Lyu, Doroodchi, Sheng, et al, 2020). Briefly, adult worms laid eggs on a plate covered with bacteria containing the unc‐62 RNAi or the EV.…”

“…Each mouse was tested three times. Thirty‐one Meis1 KO males and 28 WT males with an average age of 5 months were used in the tail‐flick test (Lyu, Doroodchi, Sheng, et al, 2020; Lyu, Doroodchi, Xing, et al, 2020; Lyu, Xing, DeAndrade, Perez, Yokoi, et al, 2020; Lyu, Xing, DeAndrade, Perez, Zhang, et al, 2020). The sample size was determined according to (Sora et al., 1997).…”

“…Six Meis1 KO males and seven WT males with an average age of 4 months were tested for wheel‐running activity (DeAndrade et al., 2012; Lyu, DeAndrade, et al, 2020; Lyu, Doroodchi, Sheng, et al, 2020; Lyu, Doroodchi, Xing, et al, 2020; Lyu, Xing, et al, 2019; Lyu, Xing, DeAndrade, Perez, Yokoi, et al, 2020; Lyu, Xing, DeAndrade, Perez, Zhang, et al, 2020). The sample size was determined according to (DeAndrade et al., 2012).…”

“…The experiment was performed as described (Lyu, DeAndrade, et al, 2019, 2020; Lyu, Doroodchi, Sheng, et al, 2020; Lyu, Doroodchi, Xing, et al, 2020). The sample size was determined according to (Lyu et al, 2019; Lyu, DeAndrade, et al, 2020; Lyu, Doroodchi, Sheng, et al, 2020; Lyu, Doroodchi, Xing, et al, 2020). The striata were dissected at 10:00 a.m. from 7 Meis1 KO males and 7 WT males with the average age of 6 months to measure TH, choline acetyltransferase (ChAT), acetylcholinesterase (AChE), choline transporter (ChT), and vesicular acetylcholine transporter (VAChT).…”