The mice of this strain have been backcrossed more than 10 backcrosses to C57BL/6J, making this strain more effective for studies of the Nos1 KO than the incipient stock (#002633).
The nitric oxide signaling molecule produced by the neuronal Nos1 gene is widely expressed, affecting diverse systems. The knockout of this gene has been shown to affect such normal functions as cognition and behavior, long-term memory, cortical development, colonic motility, skeletal muscle contractility, ovarian cycle regulation, cardiac/cardiovascular function, and certain immune system responses. Western blots of brain homogenates from homozygous mutant mice showed no detectable protein. However, splice variants are expressed and variable low levels of NOS activity are seen in the brain.
Heterozygous mice are viable and fertile, while some lethality is seen in homozygotes due to stomach hypertrophy. The first publication describing this knock-out reported that mutants have enlarged stomachs with hypertrophy of the pyloric sphincter and the circular muscle layer (Huang et al., 1993). Male homozygotes of this strain were initially reported to be more aggressive than control mice, but this has been since attributed to heterogeneity of the stock before it was sufficiently backcrossed to the C57BL/6J genetic background. The C57BL/6J-congenic strain at The Jackson Laboratory (Stock No. 002986) shows normal behavior in this regard.
The Jackson Laboratory preferred mating scheme for Stock No. 002986 is breeding heterozygous mice together, or by breeding heterozygous females to homozygous males. Breeding heterozygous mice together has resulted in variable Mendelian ratios of homozygous pups (e.g., ~10% in September 2019 but ~24% in September 2020). Of note, we attempted breeding homozygotes together and found they generated offspring at a much slower rate.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for this strain. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
