FELINE GOITEROUS CONGENITAL HYPOTHYROISISM
猫甲状腺肿先天性甲状腺功能减退症
基本信息
- 批准号:7391968
- 负责人:
- 金额:$ 0.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-08-01 至 2007-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Congenital hypothyroidism may either be caused by dysmorphogenesis of the thyroid gland (hypo- or aplasia) or by dyshormonogenesis associated with a goiter. Disorders in hormonogenesis include the inability of the thyroid to concentrate iodide, thyroglobulin deficiency, and organification defects caused by thyroid peroxidase deficiency. Congenital hypothyroidism has been described in humans and animals, including sporadic feline cases. We have studied the clinical features, endocrine and biochemical abnormalities, pathologic findings, and breeding studies of a family of domestic shorthair cats with primary congenital hypothyroidism. Month-old male and female littermates failed to thrive, had coarse facial features, stunted growth with shortened body length, and appeared constipated and dull. Bone growth was markedly delayed for the age of the animals. A diagnosis of hypothyroidism was reached based upon low serum T3 and T4 concentrations and a response to thyroxin treatment. The affected male and mother were bred which resulted in affected kittens, whereas, when out-crossed to healthy unrelated animals no affected kittens were produced. Breeding two healthy offspring of the affected cat also produced affected kittens. All affected kittens had a congenital goiter with thyroid glands of the original affected cat measuring 5 x 2 x 2 cm each and weighing 6.6 and 5.72 g despite 2 years of treatment The thyroid glands were markedly hypercellular revealing few open follicles and minimal colloid production. Immunohistochemistry was consistent with thyroid hyperplasia of follicular epithelial cells. Serum T3, free, and total T4 concentrations of affected cats were consistently low/unmeasurable, whereas serum thyroid stimulating hormone (TSH) levels were high from the first days of life when compared to healthy cats. There was no thyroid peroxidase activity in thyroid tissue from affected cats, whereas normal thyroids showed iodide oxidation activity of 1.04 ¿ 0.59 U/mg protein. In this family of domestic shorthair cats, congenital hypothyroidism with goiter was caused by a complete thyroid peroxidase deficiency and is inherited as an autosomal recessive trait. Molecular studies are underway to determine the genetic basis for the disease in this feline model. The clinical and pathologic features, endocrine basis, and mode of inheritance are homologues to the disorder seen in humans and dogs. This disease model may offer opportunities to assess the intrauterine effects of thyroid hormone, gene transfer to the thyroid gland and stem cell therapy. We are also studying two dwarf, retarded Golden retriever littermates with hypothyroidism due to a TSH deficiency suggestive of a pituitary defect. These additional disease models may offer a better understanding of the entire endocrine axis for the thyroid hormone in this species.
本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者(PI)可能已经从另一个NIH来源获得了主要资金,因此可以在其他CRISP条目中表示。列出的机构是中心的,不一定是研究者的机构。先天性甲状腺功能减退症可能是由甲状腺发育异常引起的(甲状腺发育不全或发育不全),也可能是由甲状腺肿引起的甲状腺发育异常引起的。激素生成障碍包括甲状腺不能浓缩碘、甲状腺球蛋白缺乏和甲状腺过氧化物酶缺乏引起的组织缺陷。先天性甲状腺功能减退症已在人类和动物中被描述,包括零星的猫病例。我们研究了一科患有原发性先天性甲状腺功能减退症的家养短毛猫的临床特征、内分泌和生化异常、病理表现和育种研究。月龄雄性和雌性幼崽发育不良,面部粗糙,发育迟缓,体长缩短,出现便秘和呆滞。随着动物年龄的增长,骨骼生长明显延迟。根据低血清T3和T4浓度以及对甲状腺素治疗的反应,诊断为甲状腺功能减退。受影响的公猫和母猫杂交后,产生了受影响的小猫,而与健康的不相关动物异种杂交时,没有产生受影响的小猫。饲养两只受影响的猫的健康后代也产生了受影响的小猫。所有受影响的小猫都有先天性甲状腺肿,尽管经过2年的治疗,原受影响猫的甲状腺尺寸为5 × 2 × 2厘米,重量分别为6.6和5.72 g。甲状腺明显呈细胞增多,显露出很少的开放卵泡和极少的胶体生成。免疫组化与甲状腺滤泡上皮细胞增生一致。与健康猫相比,受影响猫的血清T3、游离T4和总T4浓度一直很低/无法测量,而血清促甲状腺激素(TSH)水平从出生第一天起就很高。病猫甲状腺组织无甲状腺过氧化物酶活性,而正常甲状腺组织碘氧化活性为1.04 ~ 0.59 U/mg蛋白。在这个家养短毛猫家族中,先天性甲状腺功能减退伴甲状腺肿大是由完全甲状腺过氧化物酶缺乏引起的,并且是一种常染色体隐性遗传性状。分子研究正在进行,以确定这种猫科动物模型疾病的遗传基础。临床和病理特征、内分泌基础和遗传方式与人类和狗的疾病相似。这种疾病模型可能为评估甲状腺激素、基因转移到甲状腺和干细胞治疗的宫内效应提供机会。我们也在研究两只侏儒,弱智的金毛猎犬,由于TSH缺乏提示垂体缺陷而患有甲状腺功能减退症。这些额外的疾病模型可以更好地了解该物种甲状腺激素的整个内分泌轴。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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{{ truncateString('URS GIGER', 18)}}的其他基金
LABORATORY IDENTIFICATION OF INBORN ERRORS OF METABOLISM
先天性代谢缺陷的实验室鉴定
- 批准号:
7391944 - 财政年份:2006
- 资助金额:
$ 0.34万 - 项目类别:
PILOT PROJECT ON GENETIC DISEASES IN NON-HUMAN PRIMATES
非人类灵长类动物遗传疾病试点项目
- 批准号:
7391945 - 财政年份:2006
- 资助金额:
$ 0.34万 - 项目类别:
LABORATORY IDENTIFICATION OF INBORN ERRORS OF METABOLISM
先天性代谢缺陷的实验室鉴定
- 批准号:
7153980 - 财政年份:2005
- 资助金额:
$ 0.34万 - 项目类别: