Genetic Association of Mutation at Agouti Locus with Adrenal X Zone Morphology in BALB/c Mice

Tanaka, Shin; Kuwahara, Sachi; Nishijima, Kazutosi; Ohno, Tamio; Matsubara, Akio

doi:10.1538/expanim.55.343

Cited by 5 publications

(9 citation statements)

References 13 publications

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“…There was a possibility that Xzvdq2 was suggested to be due to agouti because some studies have suggested that the agouti locus was likely to have an effect on X-zone vacuolation [5,6]. In F 2 non- A y mice, those with the A / a genotype had a significantly higher grade of vacuolation compared with mice having a / a genotype based on the four-grade evaluation (Table 6).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, Shire and Spickett [4] reported that strain differences were a consequence of genetic variations at a single locus, “earlier X-zone degeneration locus” ( Ex ), on chromosome 7. Tanaka et al [5,6] reported a close association between X-zone morphology and the agouti locus genotype on chromosome 2. They suggested that the a allele suppressed the vacuolation of the cells in the X-zone in a dominant manner.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the A y allele is homozygous lethal; therefore living A y mice are invariably heterozygotes. DDD.Cg- A y strain was used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested [5,6]. While Tanaka et al [5,6] investigated the effect of the a , A , and A w alleles on the X-zone vacuolation, they did not investigate the effect of the A y allele.…”

Section: Introductionmentioning

confidence: 99%

“…DDD.Cg- A y strain was used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested [5,6]. While Tanaka et al [5,6] investigated the effect of the a , A , and A w alleles on the X-zone vacuolation, they did not investigate the effect of the A y allele. Comparison of X-zone morphology between B6 and B6.Cg- A y , and DDD and DDD.Cg- A y makes it possible to reveal the effect of the A y allele.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

Suto

2012

BMC Genet

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BackgroundAdrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL) analysis for the extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay mice (F2 mice with the Ay allele) and F2 non-Ay mice (F2 mice without the Ay allele). These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg-Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The Ay allele is dominant and homozygous lethal; therefore, living Ay mice are invariably heterozygotes.ResultsSingle QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8.ConclusionsThe extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone. Identifying the genes responsible for the QTLs will be essential for understanding the molecular basis of X-zone function, which is currently unclear.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

Suto

2012

BMC Genet

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“…Although it was recently reported that the agouti locus affects vacuolation [16,19], no statistical data were provided. As female DDD mice have a thicker and more vacuolated X zone than other strains of mice [18], we considered that the female DDD mice were suitable for the observation of all adrenocortical zones including the X zone.…”

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confidence: 99%

A Morphometric Study of the Adrenal Cortex of the Female DDD Mouse

Tsujio

Mizorogi

Nishijima

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. The aim of this study was to determine whether the thickness of the adrenocortical zone is associated with age in virgin and parous female DDD mice. The zona reticularis and zona glomerulosa of parous mice tended to be thicker than those of virgin mice at all ages. The zona fasciculata lactating parous mice was significantly thicker than that of virgin mice at 20 weeks of age (P<0.01). Age did not affect the thickness of the three outer adrenocortical zones in either group. However, in virgin mice, the X zone consisted of vacuolated and nonvacuolated cells at 5 weeks of age and only of vacuolated cells at 10 weeks of age; the number of vacuolated cells and the thickness of the zone decreased at 40 weeks of age. In contrast, parous mice of all ages lacked an X zone. The decrease in X zone thickness with age was most evident when expressed relative to organ weight. In conclusion, the thickness of the outer three adrenocortical zones is affected by endocrine changes associated with pregnancy and lactation but not by age. The thickness of the X zone is an index of growth and maturation in nulliparous female DDD mice less than one year of age. KEY WORDS: adrenal cortex, age, DDD mouse, reproduction, X zone morphology.The adrenal cortex of most mammals consists of three zones. These zones play distinct roles in steroid hormone production [11]. The mineral corticoid of the zona glomerulosa regulates Na-K valance. The glucocorticoid of the zona fasciculata regulates multiple physiological metabolisms, and the adrenal androgen is mainly produced in the zona reticularis (exclude mice and rats [11]). In the mouse, a fourth zone, the X zone, is present in the innermost cortex of the adrenal. Masui and Tamura first described the characteristics of this zone in 1924 [12]. It was named the X zone by Howard-Miller in 1927 [8]. Many studies have shown that degeneration of this zone is induced by pregnancy and lactation [10]. Furthermore, in the absence of pregnancy, X zone degeneration is induced by the administration of androgen [6]. In male mice, degeneration of the X zone is induced by sexual maturation [3]; and regeneration of a second X zone is induced by castration of adult mice or androgen administration [4,7]. Thus, the endocrinological characteristics of these four adrenocortical zones are well known. But, little studies have been conducted on agerelated changes in the morphology of these adrenocortical zones [1].Strain differences in the morphology of X zone degeneration have been observed between A/Cam and CBA/FaCam mice [15], C57BL/6By and BALB/cBy mice [8], C57BL/ 6JJms and DDD mice [18], and A/J and SM/J mice [19,20].The main differences between strains involve the extent of vacuolation, which is an index of tissue lipid content [15,18,20,24]. Although it was recently reported that the agouti locus affects vacuolation [16,19], no statistical data were provided. As female DDD mice have a thicker and more vacuolated X zone than other strains of mice [18], we considered that the female DDD mice were suitable...

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Oral benzo[a]pyrene‐induced cancer: Two distinct types in different target organs depend on the mouse Cyp1 genotype

Shi

Dragin

Miller

et al. 2010

Intl Journal of Cancer

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Benzo [a]pyrene (BaP) is a prototypical polycyclic aromatic hydrocarbon (PAH) found in combustion processes. Cytochrome P450 1A1 and 1B1 enzymes (CYP1A1 and CYP1B1) can both detoxify PAHs and activate them to cancer-causing reactive intermediates. Following high dosage of oral BaP (125 mg/kg/day), ablation of the mouse Cyp1a1 gene causes immunosuppression and death within~28 days, whereas Cyp1(1/1) wild-type mice remain healthy for >12 months on this regimen. In this study, male Cyp1(1/1) wild-type, Cyp1a1(2/2) and Cyp1b1(2/2) single-knockout and Cyp1a1/1b1(2/2) double-knockout mice received a lower dose (12.5 mg/kg/day) of oral BaP. Tissues from 16 different organs-including proximal small intestine (PSI), liver and preputial gland duct (PGD)-were evaluated; microarray cDNA expression and >30 mRNA levels were measured. Cyp1a1(2/2) mice revealed markedly increased CYP1B1 mRNA levels in the PSI, and between 8 and 12 weeks developed unique PSI adenomas and adenocarcinomas. Cyp1a1/1b1(2/2) mice showed no PSI tumors but instead developed squamous cell carcinoma of the PGD.

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Genetic Association of Mutation at Agouti Locus with Adrenal X Zone Morphology in BALB/c Mice

Cited by 5 publications

References 13 publications

Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

A Morphometric Study of the Adrenal Cortex of the Female DDD Mouse

Oral benzo[a]pyrene‐induced cancer: Two distinct types in different target organs depend on the mouse Cyp1 genotype

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