Withdrawal Seizure-Resistant, replicate 1 and 2 (WSR1, WSR2) mice were selectively bred to exhibit low alcohol withdrawal convulsion severity. Used in conjunction with the Withdrawal Seizure-Prone, replicate 1 and 2 (WSP1, WSP2) and control replicate 1 and 2 lines (WSC1, WSC2) they may be useful for studying the genetic and neurobiological basis of alcohol withdrawal severity.

The Withdrawal Seizure-Resistant replicate lines (WSR1 and WSR2) were selectively bred for low 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. In parallel, Withdrawal Seizure-Prone replicate lines (WSP1 and WSP2) were selectively bred for high alcohol withdrawal convulsion severity after an identical regimen of chronic exposure to ethanol and show withdrawal handling-induced convulsions. Both WSR replicate lines exhibit seizures approximately 10-fold less severe than the WSP replicate lines. Control lines (WSC1, WSC2) were generated by random matings within each replicate line. Each line consists of five families that are bred to each other by rotation. The effect is to fix alleles conferring low seizure withdrawal severity in the homozygous state, to eliminate alleles conferring high withdrawal seizure severity and to allow the rest of the genome to segregate randomly. Used in conjunction with the Withdrawal Seizure-Prone, replicate 1 and 2 (WSP1, WSP2) and the control lines (WSC1, WSC2) they may be useful for studying the genetic and neurobiological basis of alcohol withdrawal severity.

Withdrawal Seizure-Resistant, replicate 1 (WSR1) mice were selectively bred for low 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-Resistant Replicate 1 (WSR1) line the lowest 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 acombination of the 9 families to form the WSR1 line in 2016.

Wild-type littermates

The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.

John Crabbe, Ph.D., Oregon Health & Science University.