What r and F actually mean
r is the probability that, at a random locus, two individuals share an allele *by descent* — that is, inherited from the same ancestral copy, not just the same sequence. Two completely unrelated mice might share a lot of allele sequences by chance (they are both mice!), but r counts only the shared-by-descent fraction. r = 0.5 means 50% of loci are identical by descent; r = 0.125 means 12.5% (first cousins).
F is the probability that, at a random locus, an individual is *homozygous by descent* — that both of its alleles trace back to the same ancestral copy in its pedigree. For the offspring of two parents with relatedness r, F_offspring = r / 2. That is why full-sib mating (r = 0.5) gives F = 0.25: a quarter of the offspring's genome is homozygous by descent.
Inbreeding depression — reduced litter size, smaller pups, lower fertility — starts to become detectable around F 0.0625 in outbred stocks and gets progressively worse as F climbs. The NIH Guide for the Care and Use of Laboratory Animals treats the first-cousin threshold (F = 0.0625) as the practical boundary. Maintained inbred strains operate well above this by design and use the homozygosity as the whole point of the strain.