Withdrawal Seizure-Prone, replicate 1 and 2 (WSP1, WSP2) mice were selectively bred to exhibit high alcohol withdrawal convulsion severity. Used in conjunction with the Withdrawal Seizure-Resistant, replicate 1 and 2 (WSR1, WSR2) and control replicate 1 and 2 lines (WSC1, WSC2) they may be useful for studying the genetic and neurobiological basis of alcohol withdrawal severity.
John C Crabbe, Oregon Health & Science University
The Withdrawal Seizure-Prone replicate lines (WSP1 and WSP2) were selectively bred for high alcohol withdrawal convulsion severity following 72hr of continuous chronic ethanol vapor inhalation combined with the administration of pyrazole to inhibit ethanol metabolism and stabilize blood alcohol levels. Mice were evaluated for responsiveness to handling-induced convulsions. WSP1 and WSP2 mice show more severe ethanol withdrawal than any known inbred, congenic or mutant mouse strain.
In parallel, Withdrawal Seizure-Resistant replicate lines (WSR1 and WSR2) were selectively bred for low alcohol withdrawal convulsion severity after an identical regimen of chronic exposure to ethanol and show little to no withdrawal handling-induced convulsions. Both WSP replicate lines exhibit seizures approximately 10-fold more severe than the WSR replicate lines.
Control lines (WSC1, WSC2) were generated by random matings within each replicate line.
WSP1 and WSP2 also exhibit withdrawal convulsions from other sedative hypnotic drugs such as pentobarbital and diazepam. Each line consists of five families that are bred to each other by rotation. The effect is to fix alleles conferring high seizure withdrawal severity in the homozygous state, to eliminate alleles conferring low withdrawal seizure severity and to allow the rest of the genome to segregate randomly.
Used in conjunction with the Withdrawal Seizure-Resistant, replicate 1 and 2 (WSR1, WSR2) and the control lines (WSC1, WSC2) they may be useful for studying the genetic and neurobiological basis of alcohol withdrawal severity.
Withdrawal Seizure-Prone, replicate 1 (WSP1) mice were selectively bred for high alcohol withdrawal convulsion severity after 72hr of continuous chronic ethanol vapor inhalation. The founder stock for selective breeding was the HS/Ibg heterogeneous stock that was developed by Gerald McClearn and colleagues (The Institute for Behavioral Genetics, Boulder, Colorado) as an 8-way cross of the following inbred strains obtained from the Cancer Research Genetics Laboratory at UC-Berkeley: A, AKR, BALB/c, C3H/2, C57BL, DBA/2, Is/Bi, and RIII.
Eighteen matings of Generation 30 HS/Ibg mice were randomly divided into 2 groups of 9 families each. These generation 31 mice became the foundation (So) population for selection based on alcohol withdrawal severity. One group of 9 familes was designated Replicate 1, the other Replicate 2. To establish the Withdrawal Seizure-Prone Replicate 1 (WSP1) line the highest scoring male and female from each family were selected. Selected progeny from each family were then mated using a rotational system – female from Family 1 mated to male from Family 2, female from Family 2 mated to male from Family 3, etc. Two to six reserve families were generated to provide back up. The selection process was repeated for 26 generations. Relaxed breeding (random selection of breeders from within each family) has continued for approximately 100 generations. The MMRRC imported a combination of the 9 families to form the WSP1 line in 2016.
Currently there are no related genes or alleles for this strain.
The Withdrawal Seizure-Prone, replicate 1 line consists of 5 families that were combined to form the WSP1 line. This line is maintained as a closed mating system.
When using the Withdrawal Seizure-Prone 1 mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41486 in your Materials and Methods section.