Biomaterial Database

Menkes' disease: abnormal metallothionein gene regulation in response to copper. 1985

A Leone, and G N Pavlakis, and D H Hamer

Menkes' disease, an inherited disorder of copper metabolism, is characterized by the accumulation of excess copper-metallothionein in certain tissues and cell types. Using cultured fibroblasts, we show that this is due to the ability of low concentrations of copper to induce metallothionein mRNA synthesis in Menkes' but not normal cells. We also show that copper, which is unusually toxic to Menkes' cells, induces the synthesis of 84 kd and 68 kd polypeptides tentatively identified as heat shock proteins. Transfection experiments with a cloned metallothionein fusion gene show that this is due to a defect in a diffusible factor involved in either metallothionein gene transcriptional regulation or copper metabolism.

UI	MeSH Term	Description	Entries
D007706	Menkes Kinky Hair Syndrome	An inherited disorder of copper metabolism transmitted as an X-linked trait and characterized by the infantile onset of HYPOTHERMIA, feeding difficulties, hypotonia, SEIZURES, bony deformities, pili torti (twisted hair), and severely impaired intellectual development. Defective copper transport across plasma and endoplasmic reticulum membranes results in copper being unavailable for the synthesis of several copper containing enzymes, including PROTEIN-LYSINE 6-OXIDASE; CERULOPLASMIN; and SUPEROXIDE DISMUTASE. Pathologic changes include defects in arterial elastin, neuronal loss, and gliosis. (From Menkes, Textbook of Child Neurology, 5th ed, p125)	Hypocupremia, Congenital,Kinky Hair Syndrome,Menkes Syndrome,Steely Hair Syndrome,Congenital Hypocupremia,Copper Transport Disease,Kinky Hair Disease,Menkea Syndrome,Menkes Disease,Menkes' Disease,Steely Hair Disease,X-Linked Copper Deficiency,Congenital Hypocupremias,Copper Deficiencies, X-Linked,Copper Deficiency, X-Linked,Copper Transport Diseases,Deficiencies, X-Linked Copper,Deficiency, X-Linked Copper,Disease, Copper Transport,Disease, Steely Hair,Diseases, Copper Transport,Diseases, Kinky Hair,Diseases, Menkes',Diseases, Steely Hair,Hair Diseases, Kinky,Hair Diseases, Steely,Hypocupremias, Congenital,Kinky Hair Diseases,Menkea Syndromes,Menkes' Diseases,Steely Hair Diseases,Steely Hair Syndromes,Syndrome, Menkea,Syndrome, Steely Hair,Syndromes, Menkea,Syndromes, Steely Hair,Transport Disease, Copper,Transport Diseases, Copper,X Linked Copper Deficiency,X-Linked Copper Deficiencies
D008668	Metallothionein	A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals.	Isometallothionein,Metallothionein A,Metallothionein B,Metallothionein I,Metallothionein II,Metallothionein IIA
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D001928	Brain Diseases, Metabolic	Acquired or inborn metabolic diseases that produce brain dysfunction or damage. These include primary (i.e., disorders intrinsic to the brain) and secondary (i.e., extracranial) metabolic conditions that adversely affect cerebral function.	Central Nervous System Metabolic Disorders,Encephalopathies, Metabolic,Metabolic Disorders, Brain,Acquired Metabolic Diseases, Brain,Acquired Metabolic Diseases, Nervous System,Acquired Metabolic Encephalopathies,Brain Diseases, Metabolic, Acquired,Brain Disorders, Metabolic,Brain Disorders, Metabolic, Acquired,Brain Syndrome, Metabolic,Brain Syndrome, Metabolic, Acquired,CNS Metabolic Disorders,CNS Metabolic Disorders, Acquired,Encephalopathy, Metabolic, Acquired,Metabolic Brain Diseases,Metabolic Brain Diseases, Acquired,Metabolic Brain Syndrome,Metabolic Brain Syndrome, Acquired,Metabolic Brain Syndromes,Metabolic Brain Syndromes, Acquired,Metabolic Diseases, Acquired, Nervous System,Metabolic Disorder, Central Nervous System, Acquired,Metabolic Disorders, CNS,Metabolic Disorders, CNS, Acquired,Metabolic Disorders, Central Nervous System,Metabolic Encephalopathies,Nervous System Acquired Metabolic Diseases,Acquired Metabolic Encephalopathy,Brain Disease, Metabolic,Brain Disorder, Metabolic,Brain Metabolic Disorder,Brain Metabolic Disorders,CNS Metabolic Disorder,Encephalopathies, Acquired Metabolic,Encephalopathy, Acquired Metabolic,Encephalopathy, Metabolic,Metabolic Brain Disease,Metabolic Brain Disorder,Metabolic Brain Disorders,Metabolic Disorder, Brain,Metabolic Disorder, CNS,Metabolic Encephalopathies, Acquired,Metabolic Encephalopathy,Metabolic Encephalopathy, Acquired
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014158	Transcription, Genetic	The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.	Genetic Transcription