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Biomedical subjects

J G Shire

Publications and source records attributed to J G Shire.

At least 19 recordsLinked to original sources
PubMed1994

Adrenocortical dysplasia: a mouse model system for adrenocortical insufficiency.

A spontaneous autosomal recessive mutation causing disordered morphogenesis of the adrenal cortex has been identified in DW/J inbred strain mice and named adrenocortical dysplasia (acd). The acd mutant gene has been mapped just proximal to oligosyndactyly (Os) and esterase-1 (Es-1) in the central region of chromosome 8. Both male and female acd/acd mice are characterized by reduced survival, retarded growth, skin hyperpigmentation, poorly developed pelage and focal ureteral blockage leading to hydronephrosis. Morphometric measurements showed that acd/acd cortical cells and nuclei were increased sevenfold in volume; nuclei often showed a variety of inclusions. Cortical cells of acd/acd mice contained large numbers of mitochondria, smooth endoplasmic reticulum and lipid droplets characteristic of steroidogenic cells. While cortical X-zones failed to develop in acd/acd adrenals, medullary cells and nuclei were unaffected by mutant gene action. Resting serum corticosterone levels in female, but not male, mutant mice were significantly lower than in +/? normal littermates, whereas ACTH levels were significantly elevated in mutants of both sexes. Serum aldosterone levels were normal in acd/acd mice. Functional studies of adrenals cultured in vitro revealed that acd/acd adrenals secreted reduced amounts of corticosterone per pair of glands under both basal and ACTH-stimulated conditions. However, correction of the corticosterone secretion data to mg cortical mass in culture showed that the mutant cortical tissue secreted the same amount of glucocorticoid as did their +/? normal littermate glands. We conclude that the acd mutant gene acts in an unknown fashion to cause a fundamental defect in cellular proliferation in the adrenal cortex, leading to compensatory marked hypertrophy of cortical cells and grossly enlarged nuclei. The role of acd action in adrenal cortical development remains to be established.

Adrenal Cortex↗
PubMed1991

Effects of hyperprolactinemia on ornithine decarboxylase activity and polyamine levels in seminal vesicles of genetically prolactin-deficient adult dwarf mice.

Prolactin (PRL) has been shown to exert many different actions in various biological systems. Polyamines are known to influence the growth and function of the seminal vesicles (SV). Furthermore, ornithine decarboxylase (ODC) is considered a key enzyme in the biosynthesis of polyamines and is regulated by PRL in certain target tissues. Adult Ames dwarf mice (df/df), genetically deficient in PRL, were used for this study. The experimental groups were as follows: Group 1, pituitary-grafted; Group 2, sham-operated; Group 3, castrated + testosterone propionate (TP)-treated (25 micrograms/mouse, 3 times/wk, s.c.) + grafted; and Group 4, castrated + TP as above. The animals were killed 40 days later, and polyamines and ODC activity in SV and liver were determined. Serum PRL, FSH, and testosterone (T) were also measured. In the grafted groups, there were significant elevations in serum PRL and FSH levels. In the gonad-intact, pituitary-grafted group, animals exhibited an elevation in plasma T levels, and similar levels were achieved in the castrated, androgen-replaced groups. In hyperprolactinemic mice, the weights of SV were significantly greater than in the corresponding control groups. The relative weights of the SV showed a similar pattern. An increase in ODC activity was observed in both SV and liver in hyperprolactinemic groups. In those animals in which serum T levels were held constant, an increase in the enzyme activity in SV was detected in hyperprolactinemic group whereas in liver, no significant difference was observed. Concentrations of polyamines in the SV were increased in hyperprolactinemic, castrated, TP-treated mice. The present results indicate that PRL can exert a direct stimulatory effect on the growth, ODC activity, and polyamine levels in the SV.

Animals↗
PubMed1989

Lysosomal mutations increase susceptibility to anaesthetics.

The anaesthetic responses of homozygous mutant mice were compared with those of their normal heterozygous littermates. The two recessive mutations studied were beige (bg) and reduced pigmentation (rp). Homozygosity for either significantly increased the sleeping time of both sexes after treatment with pentobarbital, tribromoethanol or the steroid anaesthetic alphaxalone.

Anesthesia↗
PubMed1989

Paternal inheritance of egg traits in mice: a case of genomic imprinting.

Eggs from reciprocal hybrids between the C57BL/6By and BALB/cBy strains were tested for their susceptibility to attack by hyaluronidase and pronase. There were significant reciprocal differences between the F1 females in the responses of their unfertilized eggs to both enzymes. The F1 hybrids from BALB mothers showed the increased susceptibility characteristic of C57BL whilst the F1 hybrids with C57BL mothers were more resistant to both enzymes, like BALB mice. Eggs from the four kinds of reciprocal F2 hybrid females also showed patroclinous patterns of susceptibility. A patroclinous difference was found between reciprocal crosses of the CXBD and CXBE recombinant inbred strains but not in crosses between recombinant inbred strains with similar phenotypes. Cross fostering did not alter the phenotypes of the C57BL and BALB females or those of their reciprocal F1 hybrids. The findings are interpreted in terms of differential genomic imprinting of paternally inherited information. The possible general usefulness of patroclinous differences between reciprocal F1 females in revealing differences in imprinting is noted.

Animals↗
PubMed1989

Genotypic effects on gonadal size in fetal mice.

Fetal gonadal size was measured on Days 13, 16 and 19 of gestation in the C57BL/6ByEss (B) and BALB/cByEss (C) inbred strains, their two reciprocal F1 hybrids (CXB and BXC) and in the CXBD and CXBE recombinant inbred lines. At Day 13, CXB F1 fetuses, with C57 fathers and BALB mothers, had significantly larger testes and ovaries than did fetuses of the other 5 stocks. On Day 16, BALB fetuses had significantly larger testes than did C57, while at Day 19 C57 fetuses had significantly larger testes than did BALB fetuses. The CXB and BXC F1 fetuses had significantly larger testes than did mice of the two parental strains on Days 16 and 19, even though the mothers of all 4 kinds of fetus came from the same two inbred strains. C57 and BALB mice did not differ significantly in ovarian size, but had significantly smaller ovaries than did mice of the other genotypes on Days 16 and 19. CXBD mice had the largest ovaries, followed by those of the F1 hybrids. Ovarian size in CXBE mice was similar to that in the CXB hybrids. There were strong maternal effects on gonad size on Days 13 and 19 of gestation. The genes that influenced fetal testicular and ovarian growth appeared to differ from those expressed post-natally at 30 and 60 days.

Animals↗
PubMed1989

Genetic variation in testicular development in mice of the C57BL/10ScSn, C57BL/6By and BALB/cBy strains and the CXB recombinant-inbred lines.

When compared with C57BL/6By mice, BALB/cBy mice had testes that were 41% heavier at 60 days of age and seminiferous tubules that were 41% greater in cross-sectional area at 120 days. Absolute testicular weight did not increase between 60 and 120 days of age in either C57BL/6By or C57BL/10ScSn mice but did in BALB mice, paralleling changes in the size of the seminiferous tubules. Significant testicular growth took place over this age period in mice of all seven of the CXB recombinant-inbred (RI) strains of mice derived from a cross of the BALB/cBy and C57BL/6By strains. The wide range of phenotypes shown by adult recombinant mice, which ranged from those with significantly heavier testes than BALB to those with testes the same size (at 60 days) as those of C57BL/10ScSn mice, implied the existence of several separable factors affecting testicular size in adults. At 30 days of age the RI lines fell into two groups; one with small testes like C57BL/6By and the other with larger testes like BALB/cBy mice. The segregation pattern for prepubertal testicular weight was identical to that for the H-2 histocompatibility locus.

Animals↗
PubMed1989

Unequal parental contributions: genomic imprinting in mammals.

Evidence for genomic imprinting, in which the expression of genes is influenced by their parental origin, is provided by pronuclear transplantation experiments, by studies of X-chromosome inactivation and monoparental disomy, and by the analysis of the expression and methylation of certain transgenes. Both patroclinous and matroclinous patterns of mammalian inheritance occur, and germ-cell and gonadal traits as well as tumor development can be affected. To understand the processes that influence genetic inheritance, genomic imprinting must be distinguished from Y-linkage and cytoplasmic and other maternal effects. Genomic imprinting may be mediated by a variety of mechanisms, including DNA methylation. Further studies addressing such aspects of imprinting as its initiation and maintenance are required to understand the molecular bases for these critical genetic events.

Animals↗
PubMed1988

Genetic differences in periovum sensitivity to hyaluronidase and protease between C57BL/6, BALB and CXB recombinant mice.

The cumulus oophorus surrounding eggs from C57BL/6 mice was digested by bovine or leech hyaluronidase significantly more rapidly than that surrounding eggs from BALB/c mice. The zona pellucida of C57BL/6 eggs was also more rapidly attacked by pronase. Three other sublines of C57BL showed the same characteristics. Measurements of susceptibility to hyaluronidase and pronase on eggs from the CXB recombinant inbred strains indicated that variation at a minimum of 2 loci affected each character. The lack of correlation between susceptibilities to the 2 enzymes across the recombinant strains implied that these differences separately affect the substrates of the enzymes, rather than reflecting a common difference in the process of oocyte maturation. The variation in susceptibility was unrelated to differences, controlled by the Ped and Qa-2 loci, in the rate of later embryonic cleavage. However, pronase susceptibility was significantly correlated with the early onset of the first cleavage.

Animals↗
PubMed1987

The adrenal X-zone of mice: genetic analysis of its development with recombinant-inbred strains.

The genetic aspects of development of the adrenal X-zone in female mice have been studied in the C57BL/6By and BALB/cBy inbred strains, their hybrids, and the CXB recombinant-inbred (RI) strains. Degeneration of the X-zone, with the accumulation of sudanophilic lipid, was well established in BALB/cBy females by the age of 60 days. Degeneration occurred later in C57BL/6By females, without lipid accumulation. The F1 hybrids showed fatty degeneration at 60 days. The CXB RI strains could be divided into four groups. Two resembled the parental strains and two had recombinant phenotypes. These observations, together with those on backcrosses of RI and F1 mice to the parental strains, indicated the existence of two genes controlling X-zone development. The two loci are provisionally named Exz-1 and Exz-2. In both cases the a alleles, present in BALB, showed dominance over the b alleles, present in C57BL.

Adrenal Glands↗
PubMed1984

Persistent inverse maternal effect on corticosterone production in vitro.

Adrenal cells from C57BL/Tb mice produced more steroid than those from DBA/2J mice. Reciprocal differences between both backcross and F1 hybrids showed a persistent maternal effect. Mothers with high output produce offspring with reduced hormone production when adult. Corticosterone output thus depends on maternal phenotype as well as on the genotype of the isolated cells.

Adrenal Glands↗
PubMed1984

Studies on the inheritance of vaginal septa in mice, a trait with low penetrance.

Longitudinal vaginal septa were found in 1-3% of females of the BALB/cBy and C57BL/6By inbred strains and their F1, F2 and backcross hybrids. In the CXBJ recombinant-inbred strain over half the females were affected, showing that the parental strains differed at a minimum of 2 loci that increased the risk of septa. Crosses involving CXBJ mice showed that susceptibility could be transmitted by the male parent and suggested that the different genotypes producing low penetrance could be identified. Subline differences in C57BL were marked, the incidence ranging from 1% in C57BL/6By to about 26% in two lines congenic with C57BL/10ScSn. No association was found between incidence and H-2 histocompatibility type. Imperforate vagina occurred at a low frequency in 4 stocks in which septa were regularly found. The minor anomaly was about 15 times more likely than the malformation.

Animals↗
PubMed1984

Adrenal changes in genetically hypothyroid mice.

The adrenocortical X-zone was very poorly developed in young female mice homozygous for the hypothyroid, hyt, mutation, Feeding the mice thyroid powder resulted in the development of an X-zone. This subsequently degenerated in the same way as the X-zone found in the normal litter-mates of the mutants. We suggest that the adrenocortical effects may be due to changes in prolactin stimulation consequent upon the lack of response to thyrotrophin of the mutants.

Adrenal Cortex↗
PubMed1981

An experimental geneticist looks at catecholamine metabolism.

The contributions of genetic variation, including that at unstable and duplicated loci, interactions between alleles at different loci and genotype-environment interaction to observable phenotypic variation in experimental animals are discussed with particular reference to catecholamine metabolism. The possibilities and complexities involved in extrapolating to human populations, and to behavioural consequences of biochemical variation, are outlined.

Animals↗
PubMed1980

Corticosterone catabolism by mouse liver: interactions between genotype and diet.

Corticosterone reduction was greater in liver homogenates from C57BL/10ScSn mice than in homogenates from DBA/2J mice. The reactions were stimulated to the same extent by the addition of an NADPH-generating system when the mice had been on a 4% fat diet. When the mice had been on a fat-free diet for 3 days, the generating system produced a much greater effect on homogenates from DBA mice. C57BL/Tb mice resembled C67BL/10ScSn mice with CBA/FaCam mice were similar to DBA/2J mice.

Animals↗