title: Three new allelic mouse mutations that cause skeletal overgrowth involve the natriuretic peptide receptor C gene (Npr3).
abstract: In 1979, a BALB/cJ mouse was identified with an exceptionally long body. This phenotype was found to be caused by a recessive mutation, designated longjohn (lgj), that mapped to the proximal region of chromosome 15. Several years later, a mouse with a similarly elongated body was identified in an outbred stock after chemical mutagenesis with ethylnitrosourea. This phenotype also was caused by a recessive mutation, designated strigosus (stri). The two mutations were found to be allelic. A third allele was identified in a DBA/2J mouse and was designated longjohn-2J (lgj(2J)). Analysis of skeletal preparations of stri/stri mice indicated that the endochondral ossification process was slightly delayed, resulting in an extended proliferation zone. A recent study reported that mice overexpressing brain natriuretic peptide, one of the members of the natriuretic peptide family, exhibit a skeletal-overgrowth syndrome with endochondral ossification defects. The Npr3 gene coding for type C receptor for natriuretic peptides (NPR-C), which is mainly involved in the clearance of the natriuretic peptides, mapped in the vicinity of our mouse mutations and thus was a candidate gene. The present study reports that all three mutations involve the Npr3 gene and provides evidence in vivo that there is a natriuretic-related bone pathway, underscoring the importance of natriuretic peptide clearance by natriuretic peptide type C receptor.
authors.affiliation: Unité de Génétique des Mammifères, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: J
authors.initials: J
authors.lastname: Jaubert
authors.forename: F
authors.initials: F
authors.lastname: Jaubert
authors.forename: N
authors.initials: N
authors.lastname: Martin
authors.forename: L L
authors.initials: LL
authors.lastname: Washburn
authors.forename: B K
authors.initials: BK
authors.lastname: Lee
authors.forename: E M
authors.initials: EM
authors.lastname: Eicher
authors.forename: J L
authors.initials: JL
authors.lastname: Guénet
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001824:Body Constitution / Q000235:genetics; D001842:Bone and Bones / Q000002:abnormalities*; D002417:Cattle; D002874:Chromosome Mapping; D005808:Genes, Recessive; D006162:Guanylate Cyclase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C