CEREBELLAR HYPOPLASIA, FETAL AKINESIS, AND ARTHROGRYPOSIS IN DOGS

狗的小脑发育不全、胎儿运动不能和关节挛缩

• 批准号: 7391960
• 负责人: PAULA S HENTHORN
• 金额: $ 0.07万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/7391960
• 关键词: CEREBELLAR; HYPOPLASIA; FETAL; AKINESIS; ARTHROGRYPOSIS

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. In the same colony of dogs with congenital hypothyroidism described above, Dr. John Fyfe has identified a neurodevelopmental disorder that segregates as a fully penetrant autosomal recessive trait, lethal in utero or at birth. Affected pups lose motility during the last week of gestation and are stillborn or die at birth after a few attempts at breathing. Affected pups have quadrilateral arthogryposis, spinal scoliosis, and severe cerebellar hypoplasia. Histologic studies show loss of Purkinje and granular layer cells in the cerebellum, degenerative neurons in multiple nuclei of the CNS, and evidence of neurogenic spinal muscular atrophy. In a number of respects, this disorder resembles pontocerebellar hypoplasia with anterior horn cell involvement (PCH type I; OMIM #607596) for which no disease causing genes nor linked loci have yet been defined. Although present in the same family as the TSH-deficient dogs, the two defects segregate independently. The colony of dogs in which this disorder occurs was recently moved to Michigan State University. In the last year a collaborative proposal by Drs. Henthorn and Fyfe to NINDS has been funded to uncover the molecular basis of the CNS developmental disorder. An unrelated dog was bred to a proven carrier of the defect, and the offspring are housed at University of Pennsylvania. Breedings to determine carrier status have proven one female as a carrier and other test breedings are under way. This breeding was chosen to enhance future linkage studies by increasing heterozygousity of markers throughout the genome. We have initiated a genome scan for linkage to this disorder simultaneously with the search for a marker linked to hypothyroidism in the same family of dogs. Tentative linkage to CFA 4 has been found.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。在上述患有先天性甲状腺功能减退症的狗群中，约翰·法伊夫博士发现了一种神经发育障碍，该障碍作为完全渗透性常染色体隐性遗传特征，在子宫内或出生时致命。受影响的幼崽在妊娠最后一周失去运动能力，在几次尝试呼吸后死产或死亡。受影响的幼犬有四边形关节弯曲、脊柱侧弯和严重的小脑发育不全。组织学研究显示小脑中浦肯野细胞和颗粒层细胞的丧失、中枢神经系统多个核中神经元的退行性变化以及神经源性脊髓性肌萎缩症的证据。在许多方面，这种疾病类似于伴有前角细胞受累的脑桥小脑发育不全（PCH I 型；OMIM #607596），尚未确定其致病基因或连锁基因座。尽管与 TSH 缺陷狗属于同一家族，但这两种缺陷是独立分离的。发生这种疾病的狗群最近被转移到密歇根州立大学。去年，博士提出了一项合作提案。 Henthorn 和 Fyfe 向 NINDS 提供资助，以揭示中枢神经系统发育障碍的分子基础。一只无关的狗与已证实的缺陷携带者交配，后代被安置在宾夕法尼亚大学。确定携带者状态的育种已证明一只雌性是携带者，其他测试育种正在进行中。选择这种育种是为了通过增加整个基因组标记的杂合性来加强未来的连锁研究。我们已经启动了基因组扫描，以寻找与这种疾病的联系，同时在同一狗家族中寻找与甲状腺功能减退症相关的标记。已发现与 CFA 4 的暂定关联。