B6C3-Npr2^pwe/SacJ

Stock number: 020812
Research areas: Developmental Biology Research, Internal/Organ Research, Reproductive Biology Research

Description

Peewee (pwe) is a spontaneous mutation in Npr2 (natriuretic peptide receptor 2) a primary receptor for C-type natriuretic peptide (CNP). Mice homozygous for the mutation exhibit severe disproportionate dwarfism, a domed skull, short snout, and female infertility/male subfertility. This strain may be useful for studying skeletal dysplasia (acromesomelic dysplasia Maroteaux type (AMDM)) and female infertility.

Detailed description

NPR2 (natriuretic peptide receptor 2) is the primary receptor for C-type natriuretic peptide (CNP), which, when bound to ligand increases guanylyl cyclase activity. NPR2 is expressed in chrondocytes and osteoblasts. Mutations in NPR2 are associated with achondroplasia (ACH) and acromesomelic dysplasia Maroteaux type (AMDM). The spontaneous mutation peewee (pwe) is a 4 base pair deletion that results in a premature stop codon in the ligand binding domain. Mice homozygous for the mutation exhibit severe disproportionate dwarfism, a domed skull, short snout, and female infertility/male subfertility. Dwarfism is evident in the proximal skeleton beginning at 2 weeks of age. The femur and humerus are most affected. The skeletal defect is caused by a reduction in size of the hypertrophic and proliferative zones of the growth plate. In female mice, infertility is the result of premature oocyte meiotic resumption. This strain may be useful for studying skeletal dysplasia and female infertility.

Development

The peewee (pwe) mutation arose spontaneously on the NAW/WI background in Dr. Glen Wolfe's laboratory at the University of Kansas. Mice from the colony were transferred to Southern Illinois University and then to Dr. Sally Camper's laboratory at the University of Michigan. To maintain breeding vigor the colony has been crossed to C57BL/6J and C3H/HeJ and is maintained as a cross at every other generation to B6C3F1. The mutation has been identified as a 4 base pair deletion that alters codon 313 from leucine to a stop (L313X) in exon 3 of the ligand binding domain of natriuretic peptide receptor 2 (Npr2) gene. Upon arrival, mice were bred to B6C3F1/J (Stock #100010) for at least 1 generation to establish the colony.

Allele

Symbol: Npr2^pwe
Name: peewee
MGI accession ID: MGI:4358115
Generation method: Spontaneous
Marker symbol: Npr2
Marker name: natriuretic peptide receptor 2
Marker synonyms: AMD1; AMDM; ANPb; ANPRB; cn; ECDM; GCB; GC-B; guanylyl cyclase-B; GUC2B; GUCY2B; NPRB; NPR-B; NPRBi; pwe; SNSK
Chromosome: 4
Strain of origin: NAW
Molecular note: The peewee mutation is a 4 base pair deletion that alters codon 313 from leucine to a premature stop (L313X) in exon 3 within the ligand binding domain. The truncated protein is predicted to be nonfunctional.