Production of Sterile Mouse Model for Human and Domestic Animal

在小鼠中，由杂交种不育(HST)基因诱导的实验鼠和野生鼠之间的交配偶尔会发现种间或亚种间杂交不育。其中，Hst3基因控制了实验室小鼠与西班牙野鼠种间杂交的不育性，与X-Y染色体分离伴随中期I生精功能障碍(MI)有关。为了详细分析Hst3引起的杂交性不育，建立了携带Hst3的C57BL/6同系小鼠，直到出生后第12天，两种类型的睾丸的精子发生都相对正常。第14天，当正常睾丸出现粗线期的早期精母细胞时，不育症睾丸的粗线期精母细胞出现大量变性。20d时，正常睾丸内可见大量圆形精子细胞，而不育睾丸内未见圆形精子细胞。在性成熟日龄60天，正常的睾丸参与了各种生殖细胞，ho…根据正常和不育睾丸的形态差异，利用同种异体小鼠睾丸组织进行正常和不育睾丸的cDNA差减方法，分析正常和不育睾丸中与精子发生相关的基因。Northern印迹分析表明，部分消减克隆的转录产物在正常睾丸组织中的表达高于不育睾丸组织。其中一个克隆F77与4kb转录本在正常睾丸中的表达显著不匹配，而在不育睾丸中的表达显著高于不育睾丸。此外，除了睾丸外，其他任何器官都没有检测到该转录本。对发育中的正常睾丸和生殖细胞缺陷的W/WV突变睾丸进行的Northern杂交分析表明，CDNA克隆F77的转录本仅在正常成人睾丸中表达，而原位杂交检测到F77在细长的精子细胞和部分圆形的精子细胞中表达。C DNA克隆F77定位于小鼠8号染色体mt-1和Ctrb之间，未检测到较少的相关基因

In mice, the interspecific or intersubspecific hybrid sterility has been occasionally found in matings between laboratory mice and wild mice induced by Hybrid sterility (Hst) genes. One of them, Hst3, which controls the sterility of interspecific hybrids between laboratory mice and Mus spretus originated from Spanish wild mouse, is associated with X-Y chromosome dissociation accompanied by spermatogenic breakdown after metaphase I (MI). For detaild analysis of hybrid sterility caused by Hst3, C57BL/6 congenic mice, carring Hst3 derived from spretus, were created.Up to postnatal day 12, spermatogenesis progressed relatively normal in both type testis. At day 14, when early pachytene spermatocytes appeared in nomal testis, many degenerations weredetected on these cells in sterile testis. At day 20, many round spermatids appeared in nomal testis, while no round spermatids were found in stertile testis. At day 60 of sexually matured age, nomal testis involved in all kinds of germ cells, ho … More wever it was noted that few spermatids and spermatozoa were found in sterile testis throughout the histological sections.According to morphologial differeces between normal and sterile testis, the subtraction method between normal and sterile testis cDNA was performed using congenic mouse testis to analyze the normal spermatogenesis-associated genes. Transcripts of some subtracted cDNA clones were expressed higher in normal testis than in sterile testis by northern blot analysis. One of them, clone F77, showing significant unmatchies with entries in the demonstrated remarkable expression of apporoximately 4kb transcript in nomal testis, compared to those in sterile testis. Additionaly the transcript was not detected at any other organs except testis. Northern blot analysis using developing normal testis and germ cell-defficient W/Wv mutant testis, show that the transcript of cDNA clone F77 was expressed only in normal adult testis, in which it was detected in elongated spermatids and partially round spermatids by in situ hybridization. cDNA clone F77 was mapped at position between Mt-1 and Ctrb on mouse chromosome 8, in which no related genes were detected Less