ABSTRACT. The hypogonadic rat (hgn/hgn) shows male sterility, reduced female fertility, and renal hypoplasia, controlled by a single recessive gene located on rat chromosome 10. We developed a fine map around the hgn locus using 565 rat backcross progeny and a Rat/ Hamster radiation hybrid panel. The hgn locus was linked to Aldoc (aldolase c) and whn (winged helix of nude), and located in a 0.34-cM region between D10Rat30 and D10Rat68. The distance of the region was approximately 840-kb on rat physical map. Neither loci responsible for male sterility nor renal hypoplasia has been mapped on the homologous regions of mouse chromosome 11 and human chromosome 17. Identification of the gene responsible for the hgn mutation would provide important information on urogenital development. KEY WORDS: hypogonadism, linkage map, radiation hybrid map.J. Vet. Med. Sci. 66(9): 1151-1154, 2004 Male hypogonadic rats (hgn/hgn) show severe hypogonadism that inherited as an autosomal single recessive manner. The weight of an adult hgn/hgn testis is almost equal to that of a normal female ovary and about 1% that of a normal rat testis. These animals have small male reproductive accessory organs but no female reproductive organs [18]. Plasma testosterone is low and levels of gonadotropins are high, indicating that the cause of hypogonadism lies within the testis itself [5]. Testicular pathogenesis begins in the fetal period and progresses during postnatal testicular development [20]. Most germ cells degenerate in the testes before entering meiosis because of Sertoli cell dysfunction [13,17]. hgn/hgn males show not only hypogonadism but also bilateral hypoplastic kidney (HPK) [19]. The HPK of hgn/hgn rat contains only one-quarter the number of nephrons that are found in the normal kidney [12]. Therefore, the HPK causes chronic progressive renal failure [14]. The phenotypes of this disorder resemble those of oligomeganephronia, a congenital renal hypoplasia reported in humans [2], in respect of the reduced number of nephrons with hypertrophy of individual nephrons [12]. This combination of HPK and hypogonadism makes it possible to distinguish hgn/hgn females from phenotypically normal ones in the HGN strain [19]. hgn/hgn females identified by the presence of HPK have hypoplastic ovaries at birth, reduced reproductive performance, and early reproductive senescence [11]. Therefore, the female hgn/hgn rat is a congenital animal model of premature ovarian failure (POF) in women [9,11]. No other mutant animal showing a phenotype similar to that of the hgn/hgn rat has been reported. Therefore, the hgn/hgn rat would be a useful model for investigating the development of the mammalian reproductive and urinary organs. Our recent report revealed that the hgn locus was located in the region close to the D10Mit2 locus on rat chromosome 10 [15]; in the previous study we presented only a rough linkage map around the hgn locus, using 48 backcross progeny and 11 rat microsatellite markers. In the present study, we performed further linkage analysis us...

The hypogonadic rat () shows male sterility controlled by a single recessive gene . The females detected by the presence of renal hypoplasia in the HGN inbred strain show a reduced fertility. Recently, the gene responsible for male hypogonadism was mapped on chromosome 10 by a linkage analysis using only male backcross progeny. Because backcross females could not be categorized as affected or normal because of variations in their renal sizes, we could not examine female fertility in the backcross progeny. In the present experiment, we examined whether the gene mapped on rat chromosome 10 has any influences on female reproduction and ovarian development. The assumptive females were identified in the backcross progeny by microsatellite markers closely linked to the locus. Postnatal body growth, the weights of reproductive organs, estrus cycle and ovarian histology were examined. In addition, backcross embryos were genotyped, and their body growth and ovarian development was examined. The females showed growth retardation, a short reproductive life and an abnormal ovarian histology as adults. Regarding embryonic development, females showed body growth retardation and ovarian hypoplasia. The mutation of the mapped on chromosome 10 causes not only male sterility but also female reduced fertility related to ovarian hypoplasia beyond the altered genetic background. (Reprod Med Biol 2006; : 227-234).