Faculty Research 1990 - 1999

Three new allelic mouse mutations that cause skeletal overgrowth involve the natriuretic peptide receptor C gene (Npr3).

Document Type

Article

Publication Date

1999

Keywords

Amino-Acid-Sequence, Animal, Body-Constitution, Bone-and-Bones, Cattle, Chromosome-Mapping, Genes-Recessive, Guanylate-Cyclase, Human, Mice, Mice-Inbred-BALB-C, Mice-Mutant-Strains, Molecular-Sequence-Data, Rats, Receptors-Atrial-Natriuretic-Factor, Reverse-Transcriptase-Polymerase-Chain-Reaction, Sequence-Alignment, Sequence-Homology-Amino-Acid, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

First Page

10278

Last Page

10283

JAX Source

Proc Natl Acad Sci USA 1999 Aug; 96(18):10278-83.

Grant

GM20919/GM/NIGMS, RR01183/RR/NCRR

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.

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