ABSTRACT
Dominant negative mutations in CLCN7, which encodes a homodimeric chloride channel needed for matrix acidification by osteoclasts, cause Albers-Schönberg disease (also known as autosomal dominant osteopetrosis type 2). More than 25 different CLCN7 mutations have been identified in patients affected with Albers-Schönberg disease, but only one mutation (Clcn7G213R) has been introduced in mice to create an animal model of this disease. Here we describe a mouse with a different osteopetrosis-causing mutation (Clcn7F318L). Compared to Clcn7+/+ mice, 12-week-old Clcn7F318L/+ mice have significantly increased trabecular bone volume, consistent with Clcn7F318L acting as a dominant negative mutation. Clcn7F318L/F318L and Clcn7F318L/G213R mice die by 1month of age and resemble Clcn7 knockout mice, which indicate that p.F318L mutant protein is non-functional and p.F318L and p.G213R mutant proteins do not complement one another. Since it has been reported that treatment with interferon gamma (IFN-G) improves bone properties in Clcn7G213R/+ mice, we treated Clcn7F318L/+ mice with IFN-G and observed a decrease in osteoclast number and mineral apposition rate, but no overall improvement in bone properties. Our results suggest that the benefits of IFN-G therapy in patients with Albers-Schönberg disease may be mutation-specific.
Subject(s)
Alleles , Chloride Channels/genetics , Osteopetrosis/pathology , Animals , Bone and Bones/pathology , Cancellous Bone/pathology , Cell Count , Chloride Channels/metabolism , Disease Models, Animal , Gene Knock-In Techniques , Genes, Dominant , Heterozygote , Homozygote , Interferon-gamma/therapeutic use , Loss of Function Mutation/genetics , Mice , Organ Size , Osteoclasts/metabolism , Osteoclasts/pathology , PhenotypeSubject(s)
Abortion, Legal/trends , Abortion, Legal/supply & distribution , Eugenics , Female , Humans , Pregnancy , United StatesSubject(s)
Child Advocacy , Infanticide/legislation & jurisprudence , Life Support Care/legislation & jurisprudence , Ethics, Professional , Humans , Infant, Newborn , Medical Staff, Hospital/legislation & jurisprudence , Nursing Staff, Hospital/legislation & jurisprudence , Twins, Conjoined , United StatesSubject(s)
Abortion, Legal , Legislation, Medical , Abortion, Legal/supply & distribution , Female , Humans , Pregnancy , United StatesABSTRACT
Nearly a dozen years ago, the McGrath Thesis stimulated controversy about Catholic corporations as property owners. Though no court has ever ruled that a charitable corporation's control is vested in the general public, institutions should understand state and federal laws that affect both property ownership and its dissolution.
Subject(s)
Catholicism , Charities/legislation & jurisprudence , Financial Management/legislation & jurisprudence , Fund Raising/legislation & jurisprudence , Hospitals, Voluntary , Hospitals , Ownership/legislation & jurisprudence , Illinois , Taxes/legislation & jurisprudence , United States , UniversitiesABSTRACT
HEW funding for research involving in vitro fertilization would support acts that are ethically inappropriate and of questionable legality.
Subject(s)
Bioethics , Fertilization in Vitro , Research Support as Topic/legislation & jurisprudence , Abortion, Legal , Ethics, Medical , Fetal Viability , Financing, Government/legislation & jurisprudence , Human Experimentation , Humans , Jurisprudence , Legislation, Medical , United StatesSubject(s)
Abortion, Legal , Fetal Viability , Jurisprudence , Female , Humans , Illinois , Pregnancy , Professional Practice/standards , UtahABSTRACT
That living will, or natural death, legislation--which is currently being pushed in state assemblies nationwide--is unnecessary and may actually inhibit physicians in providing the best of care to dying patients is evident from an analysis of the statutes that have been passed. Whether the motivation behind such legislation is to take a step toward legalizing euthanasia is an open question.
