&lt;I&gt;rdw&lt;/I&gt; Rats, a New Hereditary Dwarf Model in the Rat

Koto, Masao; Sato, Tsuyoshi; Okamoto, Michio; Adachi, Jiro

doi:10.1538/expanim1978.37.1_21

Cited by 29 publications

(33 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…rdw rats were derived from the Wistar-Imamichi strain as described elsewhere (Koto et al 1988). The animals were maintained at the laboratory animal facility of Kitasato University School of Medicine.…”

Section: Animals and Tissue Treatmentmentioning

confidence: 99%

Unfolded protein response is involved in the pathology of human congenital hypothyroid goiter and rat non-goitrous congenital hypothyroidism

Барышев¹,

Sargsyan²,

Wallin³

et al. 2004

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The unfolded protein response (UPR) is an intracellular signaling pathway that regulates the protein folding and processing capacity of the endoplasmic reticulum (ER). The UPR is induced by the pharmacological agents that perturb ER functions but is also activated upon excessive accumulation of the mutant secretory proteins that are unable to attain correct three-dimensional structure and are thus retained in the ER. Such defects in intracellular protein transport underlie the development of a number of phenotypically diverse inherited pathologies, termed endoplasmic reticulum storage diseases (ERSD). We have studied UPR development in two similar ERSDs, human congenital goiter caused by the C1264R and C1996S mutations in the thyroglobulin (Tg) gene and non-goitrous congenital hypothyroidism in rdw dwarf rats determined by the G2320R Tg mutation. In both cases, these mutations rendered Tg incapable of leaving the ER. A major ER chaperone immunoglobulin-binding protein (BiP), and a novel putative escort chaperone endoplasmic reticulum protein 29 KDa (ERp29) were found to be associated with Tg, which might be interpreted as the contribution of the quality control machinery to the previously shown retention of Tg in the ER. We have extended our earlier observations of ER chaperone induction with the identification of the additional ER (ERp29, ERp72, calreticulin, protein disulfide isomerase (PDI)), cytoplasmic (heat shock protein (HSP)70, HSP90) and mitochondrial (mtHSP70) upregulated chaperones and folding enzymes. Activation of the transcriptional arm of UPR, as judged by the appearance of the spliced (active) form of X-box binding protein (XBP1) and processed activating transcription factor 6 (ATF6) transcription factors was suggested to contribute to the overexpression of the ER chaperones. The processing of ATF6 was observed in both human and rat tissues with Tg mutations. Whereas, in human tissues, weak splicing of XBP1 mRNA was detected only in the C1264R mutant, all rat thyroids including wild-type contained significant amounts of the spliced form of XBP1 as opposed to human liver and rat brain tissues, implying the existence of a previously unknown tissue-specific regulation of XBP1 processing.

show abstract

Section: Animals and Tissue Treatmentmentioning

confidence: 99%

Unfolded protein response is involved in the pathology of human congenital hypothyroid goiter and rat non-goitrous congenital hypothyroidism

Барышев¹,

Sargsyan²,

Wallin³

et al. 2004

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…Hypothyroidism reduces the weight of the adrenals [5,12] and the plasma concentration of corticosterone, and also affects circadian adrenocortical rhythm [8]. We have reported that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH [12][13][14]16] mediated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus [13].The WIC-Tg rdw (rdw) rat is a hereditary hypothyroid strain which was isolated as a dwarf model from a closed colony of Wistar-Imamichi (WIC) rats [7,18,19]. Previous reports have mainly examined reproductive functions [2-4] and the abnormalities of the thyroglobulin gene [1,9,10].…”

mentioning

confidence: 99%

“…The WIC-Tg rdw (rdw) rat is a hereditary hypothyroid strain which was isolated as a dwarf model from a closed colony of Wistar-Imamichi (WIC) rats [7,18,19]. Previous reports have mainly examined reproductive functions [2][3][4] and the abnormalities of the thyroglobulin gene [1,9,10].…”

mentioning

confidence: 99%

Pituitary-Adrenal Functions in a Hereditary Hypothyroid (rdw) Rat

et al. 2010

View full text Add to dashboard Cite

Abstract:The rdw rat is a hereditary hypothyroid strain isolated from Wistar-Imamichi rats. In the present study, adrenocorticotropic hormone (ACTH) and corticosterone responses to restraint stress (120 min) were examined in rdw adult male rats. ACTH response to restraint stress was higher in rdw rats than in hetero control rats. The plasma concentrations of corticosterone were lower in rdw rats than in control rats during the first 30 min after the onset of stress. Both ACTH and corticosterone responses to restraint stress in rdw rats recovered to control levels after thyroxine (T4) replacement therapy. These results suggest that hereditary hypothyroidism causes adrenal dysfunction directly and that hypersecretion of ACTH is a result of reduced corticosterone in rdw rats. Key words: ACTH, corticosterone, hypothyroid A. Tohei, Laboratory Animal Research Center, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Japan Thyroid hormone has been reported to play an important role in adrenal function [16]. Hypothyroidism reduces the weight of the adrenals [5,12] and the plasma concentration of corticosterone, and also affects circadian adrenocortical rhythm [8]. We have reported that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH [12][13][14]16] mediated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus [13].The WIC-Tg rdw (rdw) rat is a hereditary hypothyroid strain which was isolated as a dwarf model from a closed colony of Wistar-Imamichi (WIC) rats [7,18,19]. Previous reports have mainly examined reproductive functions [2-4] and the abnormalities of the thyroglobulin gene [1,9,10]. There has been no study investigating the pituitary-adrenal functions in the rdw rat, although hypothyroidism is known to cause adrenal dysfunction.To investigate the effect of hereditary hypothyroidism on the pituitary-adrenal function, we examined the plasma concentrations of ACTH and corticosterone in response to restraint stress for 2 h in the present study. The rdw rats and normal littermates (Wistar-Imamichi) were produced by mating adult F 1 male and female rats, as previously reported [2][3][4]. Adult (12-15 weeks old) male rdw and age-matched hetero control (+/-) rats were used in the present study. The thyroid and adrenal func--Note-

show abstract

“…Cleavage is indicative of the mutant allele, whereas wild-type alleles remain uncleaved. However, this PCR-RFLP (restriction fragment length polymorphism) assay can be problematic because failed or Tochigi, Japan The rat carrying the rdw mutation (rdw rat) was discovered in a closed colony of Wistar-Imamichi rats as a hereditary dwarf, and was established as an inbred strain [1]. The mutation is autosomal recessive [1] and causes hypothyroidism [2].…”

mentioning

confidence: 99%

“…However, this PCR-RFLP (restriction fragment length polymorphism) assay can be problematic because failed or The rat carrying the rdw mutation (rdw rat) was discovered in a closed colony of Wistar-Imamichi rats as a hereditary dwarf, and was established as an inbred strain [1]. The mutation is autosomal recessive [1] and causes hypothyroidism [2]. The gene responsible for this mutation encodes thyroglobulin, which is a key molecule in the biosynthesis of thyroid hormone, and the mutation is a G to C single nucleotide change (G6958C), resulting in a G2320R missense mutation in the acetylcholinesterase-like domain [3,4].…”

mentioning

confidence: 99%

Determination of the rdw Rat Genotype by Polymerase Chain Reaction with Allele-Specific Primer (PCR-ASP).

2004

View full text Add to dashboard Cite

Abstract:The rat carrying the rdw mutation (rdw rat) is a dwarf mutant with hypothyroidism that is caused by a single G to C transversion in the thyroglobulin gene. Therefore, the development of a simple method for molecular-based genotyping of this mutation has been problematic. We have developed a rapid and simple genotyping method that provides identification of both the rdw and wild-type allele. This polymerase chain reaction with an allele-specific primer (PCR-ASP) method amplifies only the specific allele, wild or mutant type, by using 3'-terminal mismatched primers that pair only with the respective alleles. This assay should be of value for rdw colony control and rapid discrimination of rdw/rdw, rdw/+ and +/+ rats. Key words: genotyping, rdw rat, thyroglobulin Therefore, genotyping by a molecular analytical method is indispensable for experiments on the rats before they show their phenotypes, such as characterization at preor post-natal stages and pre-implantation genetic diagnosis.The rdw mutation creates a restriction enzyme MboIsensitive site, which forms the basis of a previously developed method for molecular analysis [3]. Briefly, the region containing the rdw mutation is amplified by PCR, digested with MboI, and assayed by gel electrophoresis. Cleavage is indicative of the mutant allele, whereas wild-type alleles remain uncleaved. However, this PCR-RFLP (restriction fragment length polymorphism) assay can be problematic because failed or Tochigi, Japan The rat carrying the rdw mutation (rdw rat) was discovered in a closed colony of Wistar-Imamichi rats as a hereditary dwarf, and was established as an inbred strain [1]. The mutation is autosomal recessive [1] and causes hypothyroidism [2]. The gene responsible for this mutation encodes thyroglobulin, which is a key molecule in the biosynthesis of thyroid hormone, and the mutation is a G to C single nucleotide change (G6958C), resulting in a G2320R missense mutation in the acetylcholinesterase-like domain [3,4].For the ordinary breeding of rdw rats, it is necessary to intercross heterozygous rats or cross heterozygous female rats with thyroxine-treated homozygous male rats [5], due to the infertility of rdw rats of both sexes.

show abstract

<I>rdw</I> Rats, a New Hereditary Dwarf Model in the Rat

Cited by 29 publications

References 12 publications

Unfolded protein response is involved in the pathology of human congenital hypothyroid goiter and rat non-goitrous congenital hypothyroidism

Unfolded protein response is involved in the pathology of human congenital hypothyroid goiter and rat non-goitrous congenital hypothyroidism

Pituitary-Adrenal Functions in a Hereditary Hypothyroid (rdw) Rat

Determination of the rdw Rat Genotype by Polymerase Chain Reaction with Allele-Specific Primer (PCR-ASP).

Contact Info

Product

Resources

About