A NOVEL FUNCTIONAL-ROLE FOR APOLIPOPROTEIN-B IN MALE-INFERTILITY IN HETEROZYGOUS APOLIPOPROTEIN-B KNOCKOUT MICE

Male infertility, affecting as many as 10% of the adult population, is an extremely prevalent disorder, In most cases, the cause of the cond ition is unknown, and genetic factors that might affect male fertility , other than some sequences on the Y chromosome, have not been identif ied, We report here that male mice heterozygous for a targeted mutatio n of the apolipoprotein B (apo B) gene exhibit severely compromised fe rtility, Sperm from these mice failed to fertilize eggs both in vivo a nd in vitro, However, these sperm were able to fertilize eggs once the zona pellucida was removed but displayed persistent abnormal binding to the egg after fertilization, Irt vitro fertilization-related and ot her experiments revealed reduced sperm motility, survival time, and sp erm count also contributed to the infertility phenotype, Recognition o f the infertility phenotype led to the identification of apo B mRNA in the testes and epididymides of normal mice, and these transcripts wer e substantially reduced in the affected animals, Moreover, when the ge nomic sequence encoding human apo B was introduced into these animals, normal fertility was restored. These findings suggest that this genet ic locus may have an important impact on male fertility and identify a previously unrecognized function for apo B.