Expression of mRNA coding for pituitary hormones and pituitary-specific transcription factor in the pituitary gland of the rdw rat with hereditary dwarfism

Shibayama, K; Ohyama, Yukako; Ono, M.; Furudate, Sen-ichi

doi:10.1677/joe.0.1380307

Cited by 17 publications

(10 citation statements)

References 24 publications

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“…Shibayama et al reported a spontaneous dwarf rat originating from a Wistar Imamichi closed colony [23]. Suzuki et al reported a novel gene of rat dwarfism from Wistar Imamichi rats [25].…”

Section: Discussionmentioning

confidence: 99%

Phenotype-Based Search of Natural Mutations Related to Hereditary Diseases Existing in a Closed Colony of Mice

et al. 2010

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Abstract:We attempted to detect natural mutations existing in the Jcl:ICR closed colony of mice which is maintained by random mating. We used ordinary genetic backcrosses to efficiently detect recessive mutations carried by individual mice in the colony. Crosses of DBA/2 females and ICR males were performed to obtain F 1 mice. Four F 1 females randomly selected from each cross were backcrossed to the male parent. More than thirty backcross progeny were obtained from each F 1 female by several deliveries. Phenotypes of the backcross progeny were observed macroscopically at about one month of age. As a result, 18 (26.1%) of 69 Jcl:ICR males carried 11 recessive mutation(s). Based on the phenotypes, the tentative names were abnormal kidney, aplasia of eyelids/hind limb digits, circling, dwarfism, heterotaxy, hind limb paralysis, hydrocephalus, rigidity (or rigor), testicular hypoplasia, tremor, and wobbling. The genes responsible for aplasia of eyelids/hind limb digits and dwarfism were each carried by two males, the genes responsible for hydrocephalus and testicular hypoplasia were each carried by three males and the gene responsible for wobbling by four males. It was strongly suggested that the genes shared by several males originated from an identical mutated gene. Surprisingly, male No. 43 had the responsible genes of abnormal kidneys and testicular hypoplasia, and No. 79 had those of dwarfism and tremor. The results obtained in this study suggest that breeders need to be aware of the presence of natural mutations in their colonies.

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“…Shibayama et al reported a spontaneous dwarf rat originating from a Wistar Imamichi closed colony [23]. Suzuki et al reported a novel gene of rat dwarfism from Wistar Imamichi rats [25].…”

Section: Discussionmentioning

confidence: 99%

Phenotype-Based Search of Natural Mutations Related to Hereditary Diseases Existing in a Closed Colony of Mice

et al. 2010

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“…In the rdw rat, the thyroxine (T 4 ) levels in serum are drastically decreased [19,21,23], but the thyroid-stimu-…”

Section: Abstract: Growth Rdw Rat Thyroid Therapymentioning

confidence: 99%

“…Rat Pit-1 cDNA (826 bp) corresponding to nucleotides 104 to 928 [10] was prepared. Rat TSHβ cDNA was made by the RT-PCR method using poly (A)+ RNA prepared from normal rat pituitaries as the template and cloned into pUC118 [21]. Human glyceraldehyde-3 phosphate dehydrogenase (G3PDH) cDNA was obtained from Clontech (Palo Alto, CA, USA).…”

Section: Probesmentioning

confidence: 99%

“…On the basis of an immunohistochemical analysis, the same researchers suggested that the rdw dwarfism was caused by hypoplasia of the pituitary gland. Subsequently, it was revealed that the expressions of mRNA (Received 28 February 2005 / Accepted 1 September 2005 Address corresponding: S. Furudate, Department of Laboratory Animal Science, Japan of growth hormone (GH) and prolactin (PRL) in the rdw rat are drastically decreased [18,21]. In addition, the GH and PRL proteins in the rdw rat are decreased to a level 1/30 to 1/100 of those of a normal rat [17,18].…”

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confidence: 99%

“…Subsequently, it was revealed that the expressions of mRNA (Received 28 February 2005 / Accepted 1 September 2005 Address corresponding: S. Furudate, Department of Laboratory Animal Science, Japan of growth hormone (GH) and prolactin (PRL) in the rdw rat are drastically decreased [18,21]. In addition, the GH and PRL proteins in the rdw rat are decreased to a level 1/30 to 1/100 of those of a normal rat [17,18].In the rdw rat, the thyroxine (T 4 ) levels in serum are drastically decreased [19,21,23], but the thyroid-stimu- …”

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confidence: 99%

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Rescue from Dwarfism by Thyroid Function Compensation in rdw Rats

Furudate

Ono

Shibayama³

et al. 2005

Exp. Anim.

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The rdw rat was initially reported as having hereditary dwarfism caused by pituitary dysfunction. Subsequent studies on the rdw rat, however, have demonstrated that the primary cause of rdw dwarfism is present in the thyroid gland but not in the pituitary gland. The primary cause of rdw rat disorders is a missense mutation of the thyroglobulin (Tg) gene by a one-point mutation.In the present study, we attempted to rescue the dwarfism of the rdw rats using a diet supplemented with thyroid powder (T-powder) and a thyroid graft (T-graft). The infants of the rdw rat were successfully raised to a mature stage body weight, accompanied by elevation of serum growth hormone (GH) and prolactin (PRL), by the T-powder. Furthermore, the T-graft successfully increased the body weight with fertility. The serum GH and PRL levels in the T-graft rdw rat significantly increased. The serum thyroid-stimulating hormone (TSH) levels in the T-graft rdw rat were significantly decreased but were significantly higher than those in the control rat. The GH and PRL mRNA expression in the rdw rat with the T-graft was virtually the same as that of the control, but the TSH β mRNA differed from that of the control rats. Thus, the dwarfism in the rdw rat is rescued by thyroid function compensation, such as that afforded by T-powder and T-graft. Key words: growth, rdw rat, thyroid therapyThe rdw rat (gene symbol: rdw/rdw) was raised by Koto et al. [13] from a closed colony of the Csk: WistarImamichi strain as a variant with pituitary dysfunction. On the basis of an immunohistochemical analysis, the same researchers suggested that the rdw dwarfism was caused by hypoplasia of the pituitary gland. Subsequently, it was revealed that the expressions of mRNA (Received 28 February 2005 / Accepted 1 September 2005 Address corresponding: S. Furudate, Department of Laboratory Animal Science, Japan of growth hormone (GH) and prolactin (PRL) in the rdw rat are drastically decreased [18,21]. In addition, the GH and PRL proteins in the rdw rat are decreased to a level 1/30 to 1/100 of those of a normal rat [17,18].In the rdw rat, the thyroxine (T 4 ) levels in serum are drastically decreased [19,21,23], but the thyroid-stimu-

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Missing secretory granules, dilated endoplasmic reticulum, and nuclear dislocation in the thyroid gland ofrdw rats with hereditary dwarfism

2000

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Previous studies on the rdw rat have suggested that its dwarfism is caused primarily by dysfunction of the thyroid gland. In this study, rat thyroid glands were analyzed endocrinologically and morphologically to clarify the primary cause of dwarfism in the rdw rat. The rdw rat showed lowered thyroid hormone (T4 and T3) levels but elevated TSH in serum. The rdw thyroid gland was almost proportional in size and it was not goiter in gross inspection. Our histological investigation produced three results that may lend important evidence in understanding the problem in the thyroid gland of rdw rats. First of all, secretory granules could not be detected in the follicular epithelial cells of the rdw. Secondly, thyroglobulin was found at very low levels in the follicular lumen by immunohistochemical analysis. In contrast, it could be detected in a substantial quantity inside the dilated rER and in the huge vacuoles that are formed by swelling of the rough endoplasmic reticulum (rER) at the basal side of the follicular epithelial cells. Additionally, the nucleus of the follicular epithelial cells was pressed to the luminal side by the enlarged rER. These morphological changes would indicate that the transport of thyroglobulin is stopped at or before the formation of the secretory granules and thyroglobulin is not secreted into the follicular lumen. The rdw characterization strongly supports that rdw dwarfism is induced by hypothyroidism due to some defect(s) in the thyroid gland.

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Expression of mRNA coding for pituitary hormones and pituitary-specific transcription factor in the pituitary gland of the rdw rat with hereditary dwarfism

Cited by 17 publications

References 24 publications

Phenotype-Based Search of Natural Mutations Related to Hereditary Diseases Existing in a Closed Colony of Mice

Phenotype-Based Search of Natural Mutations Related to Hereditary Diseases Existing in a Closed Colony of Mice

Rescue from Dwarfism by Thyroid Function Compensation in rdw Rats

Missing secretory granules, dilated endoplasmic reticulum, and nuclear dislocation in the thyroid gland ofrdw rats with hereditary dwarfism

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