鈴木 浩悦

ElマウスはddYマウス由来の反射性癲癇モデル動物である。飼育観察で、Elマウスの癲癇発作が聴覚刺激により誘発される可能性が示唆された。著者らは聴覚脳幹誘発反応(ABR)に着目し、系統間、日令間および雌雄間での潜時、振幅および波形パターンを比較し、両系統の聴覚刺激に対する応答の差異を解析した。既報に従って、脳硬膜上に4つの電極を設置し、脳波を導出した。クリック音刺激を与え、同期したEEGを1024回加算した。同一個体および群内で4つの電極間でピーク潜時に変化がなく、振幅は前頭部<後頭部、ピーク潜時は180日令<70日令、雌<雄およびEl<ddYであることが明らかになった。

著者らの教室ではてんかんモデル動物(マウス、ラット)が系統維持されている。これまでにこれらの動物からの脳波導出法や解析法などの研究が行われてきた。てんかん発作の原因については不明な点が多いが、飼育中にてんかん発作を起こした動物の鳴き声から他の動物たちに発作が広がっていくことや数回放り投げることにより発作を生ずることなどが観察されている。てんかん発作と聴覚反応の関係を解明する手がかりとして聴覚脳幹誘発電位(ABR)をマウスで記録した。本実験では、電位導出には当教室で開発された関電極が脳硬膜上に配置される手法を用い、てんかんを発症するElマウスとその母系であるてんかん非発症のddYマウスについてクリック音刺激後10msecのEEGを1024回加算して得られたABRを比較した。その結果、再現性の高いABRが記録され、ピークの潜時の日齢による推移に系統間の差が見られたので報告する。

In rats with genetically hypoplastic kidneys (hpk/hpk) and associated hypogonadism (hgn/hgn), their kidneys contain only one quarter the number of nephrons that are found in those of normal rats [26]. Not surprisingly, therefore, renal excretive function has been shown to be depressed in hpk/hpk rats [26]. In the study presented here, we have examined the process of the progression of renal failure and the development of renal secondary disease in hpk/hpk rats. The plasma concentrations of urea-nitrogen and creatinine were significantly higher in adult hpk/hpk rats than in normal rats. These values elevated gradually and the degree of renal histological damage also progressed with advancing age in the hpk/hpk rats. In addition, renal anemia appeared at 140 days of age or later in these rats, and hyperplasia of the parathyroid glands was visible macroscopically at 280 days of age. In the hpk/hpk rats plasma levels of calcium and phosphorus were significantly lower and higher than in normal rats, respectively, at 280 days of age. Pathologically, the left femora of hpk/hpk rats exhibited fibrous osteodystrophy at 280 days of age and the calcium content of the right femora (as a percentage of the dry weight of bone) was significantly lower than in normal rats at both 210 and 280 days of age. These results indicate that the reduced nephrogenesis of the hpk/hpk rats causes progressive renal failure, secondarily inducing anemia, hyperparathyroidism, and osteodystrophy.

In male hypogonadic mutant rat (hgn/hgn), gonocytes degenerate and peritubular cells form multiple layers around seminiferous tubules during early postnatal testicular development. Alkaline phosphatase (AP) activity has been used as not only a tracer for the primordial germ cells (PGCs) but also a histochemical marker for the peritubular myoid cells. In the present study, we examined the localization of AP activity during the postnatal testicular development in the hgn/hgn and phenotypically normal (+/+ or +/hgn) rat. In the normal testis, high AP activity was located in the surface of the PGCs on 3 days of age. As the PGCs differentiated into spermatogonia, the AP activity drastically decreased in intensity on 7 days and was completely lost by 12 days. In the hgn/hgn, the PGCs showing high AP activity occupied the inside of dilated seminiferous tubules on 3 and 7 days of age. The luminal AP activity declined gradually by 18 days and disappeared on 21 days, when the germ cells completely degenerated in the hgn/hgn testis. In the normal, high AP activity emerged in a layer of the peritubular cells surrounding the tubules on 7 days and afterwards, indicating that the peritubular cells were differentiating into myoid cells. In the hgn/hgn, the peritubular cells formed multiple layers around the tubules and showed weak AP activity on 3 to 18 days of age. On 21 days of age, high AP activity emerged in a single layer of the peritubular cells directly attached to the basement membrane in the hgn/hgn. These results indicate that the PGCs showing AP activity kept remained at later stage in the hgn/hgn and that the single layer of mature myoid cells showing high AP activity appeared much later in the hgn/hgn testis than in normal.

The male hypogonadic rat (hgn/hgn) is accompanied with bilateral hypoplastic kidney (HPK; hpk/hpk) [34]. In this study, we examined the kidney weight (KW), glomerular number (GN), renal pathohistology at adult (80 days of age), and pathogenesis during the early postnatal stage in the hpk/hpk, +/hpk, and +/+ rat. The GN of adult hpk/hpk was significantly less than that of the +/hpk and +/+. Histologically, there were the decreased number of nephrons and the associated secondary changes in the hpk/hpk kidney. The plasma concentrations of urea nitrogen and creatinine were significantly higher in the hpk/hpk than in the +/hpk and +/+. During early postnatal stage, the KW of the hpk/hpk was significantly smaller than those of the +/hpk and +/+, and the GN was fewer in order of the hpk/hpk, +/hpk and +/+, showing the significant differences between given genotypes. The layer of nephrogenic nephron beneath the renal capsula of the neonatal kidney appeared to be thinner in the hp/hpk than in the normal (+/hpk and +/+). In the hpk/hpk kidney on 3 days of age, the layer of the nephrogenic nephron was absent in some portions beneath the renal capsula. In the hpk/hpk kidney on 7 days of age, further, the layer of immature type of nephron was still observed under the capsula. These studies suggest that the hypoplastic kidney, which may result from reduced nephrogenesis, could not compensate the renal weight, GN and renal function during the postnatal nephrogenic stage.

In order to determine the initial alterations in histopathological and hormonal milieu in the male hypogonadism mutant rats (gene symbol: hgn, a single autosomal recessive trait), postnatal morphological development of the affected testis, and testicular testosterone (T) contents, plasma concentrations of T., follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) were examined in the hgn/hgn and phenotypically normal male littermates {+/?) on days 0 to 21 after birth. The processes of postnatal differentiation of seminiferous tubules from primitive sex cords inhibition of germ cells entering mitosis, proliferation and distribution of the Sertoli cells, colonization of the gonocyte and elongation of the tubules, were defective in the hgn/hgn testis. These histopathological alterations were present at birth. These defects might result in the loss of normal spermatogonia, leading failure of spermatogenesis in the adult. Severe progressive degenerations were observed in the tubular diameter and cells within the tubules on day 7 and afterwards, and the affected status seen in the adult was achieved by day 18. There have been marked elevations in the plasma FSH and LH levels from early postnatal age in the hgn/hgn male rat, while testicular and plasma T contents and PRL values were almost comparable between hgn/hgn and +/?. © 1993, THE SOCIETY FOR REPRODUCTION AND DEVELOPMENT. All rights reserved.

The male hypogonadism rat (hgn/hgn) shows a characteristic male sterility as a single autosomal recessive trait. Recently, the female homozygotes for hgn, assumed to be fertile, could be detected by a /jgji‐associated hypoplastic kidney (hpk/hpk). The present study was to investigate a possible influence of the hgn gene on female reproduction. The hgn/hgn females showed a significant growth retardation as compared with the phenotypically normal ones (+/? +/hgn or +/+). The litter size at birth and number of implantation traces were significantly less in the hgn/hgn than in the +/? females. The hgn/hgn females became anestrous and infertile much earlier than the +/? did. Histologically, there were a few corpora lutea, some atretic follicles at different stages of maturation and abundant abnormal interstitial cells with pyknotic or karyorexic nuclei in the ovaries of hgn/hgn females that have been infertile. The birth rate expressed by per cent litter size at birth against number of implantation traces was comparable between the hgn/hgn and the +/? female, suggesting that the small litter size of hgn/hgn female could not be due to the embryonic death in utero. Nevertheless, the number of the tubal ova at estrous was comparable in the hgn/hgn and +/? females. Therefore, it was suggested that the half of ova or embryos may be lost during the period from the fertilization to the implantation. Histological appearances of the neonatal ovary in the hgn/hgn seemed hypoplastic. The number of cells including oocytes and interstitial cells, enzymatically separated from neonatal ovary, was significantly less in the hgn/hgn than in the +/hgn. These results suggest that the gene product(s) coded by normal allele of hgn gene(s) involves normal gonadal development in both sexes the defect may lead testicular dysmorphology in the male and reduced fertility in the female. Copyright © 1992, Wiley Blackwell. All rights reserved

Abstract Bilateral hypoplastic kidneys have been found to associate with the male hypogonadism rat (hgn/hgn). The hypoplastic kidney was persistent to the male homozygote for hgn and it was also seen in some females with unknown genotype. The affected kidney was apparently smaller in size than phenotypically normal one. When females with hypoplastic kidney were mated to proven heterozygous males for hypogonadism (hgn/+), the ratio of the affected testis to phenotypically normal one was 32: 20 in the Fl generation. This segregation ratio did not deviate siginificantly from the 1: 1 ratio expected from the hypothesis that the genotype of females with hypoplastic kidney in parent generation for hypogonadism would consist of hgn/hgn alone. The ratio expected from the other hypotheses was denied statistically. The ratio of the affected kidney to phenotypically normal one in both sexs of the Fi was 53: 50, fitting to 1: 1 hypothesis for a single autosomal recessive trait. There was neither a case showing the phenotypically normal kidney with the affected testis, nor the hypoplastic kidney with the phenotypically normal testis. The results suggest that the gene responsible for the hypoplastic kidney and the gene for hypogonadism would be identical or both genes reside in the close vicinity in a chromosome. The results also suggest that the homozygotes for hgn can be selected by the presence of hypoplastic kidney. Copyright © 1991, Wiley Blackwell. All rights reserved