Gene trap mutation of murine Outer dense fiber protein-2 gene can result in sperm tail abnormalities in mice with high percentage chimaerism

XL169 ES cells have a β-geo gene trap cassette inserted in the Odf2 gene. To determine possible underlying mechanisms resulting in infertility we analyzed epididymal sperm and observed that >50% displayed bent tails. We next performed ultrastructural analyses on testis of high percentage XL169 chimaeric mice. This analysis showed that high percentage XL169 chimaeric mice produce elongating spermatids that miss one or more entire outer dense fibers in their midpiece and principal piece. In addition, we observed elongating spermatids that show thinning of outer dense fibers. No other obvious abnormalities or defects are present in elongating spermatids. Spermatozoa from the caput and cauda epididymis of XL169 mice of high percentage chimaerism show additional tail defects, including absence of one or more axonemal microtubule doublets and bent tails. Sperm with bent tails display abnormal motility.Our results document the possible impact of loss of one Odf2 allele on sperm tail structure and function, resulting in a novel sperm tail phenotype.The mammalian sperm tail contains several unique structures of poorly defined function. One of these structures, the outer dense fibers (ODF), is present in the sperm tail midpiece -together with the mitochondrial sheath- as well as the principal piece. Several major ODF proteins, including Odf1 and Odf2, have now been cloned by us and others [1-6], as have proteins that associate with these major ODF proteins. Our earlier work indicated that many ODF proteins and ODF-associated proteins interact using specific leucine zipper motifs [2,7,8]. Following on these studies it was discovered that some, but not all, ODF- and ODF-associated proteins, including Odf2 [9,10], are expressed in spermatids as well as in somatic cells.Odf2 was discovered in our lab by virtue of its functional interaction with Odf1 [2]. Odf2 is a major ODF protein that can also self-interact. It has two leucine zipper motifs [2,6], one of which binds Odf1. The i