B6;129S-P3h1^tm1.1Brle/J

Stock number: 024531
Research areas: Developmental Biology Research, Internal/Organ Research

Description

This strain carries an H662A mutation in the catalytic site of the mouse Lepre1 gene. This model recapitulates elements of the bone phenotype of Osteogenesis Imperfecta (OI), but not the cartilage and growth phenotypes caused by the loss of the prolyl 3-hydroxylation complex.

Detailed description

Mutations in prolyl 3-hydroxylase 1 (P3H1), encoded by the human LEPRE1 gene (leprecan 1 or leucine proline-enriched proteoglycan 1), have been associated with recessive Osteogenesis Imperfecta (OI).

This strain carries H662A (histidine to alanine) mutation in a catalytic site of the mouse Lepre1 gene. Expression of protein in bone does not appear to be affected, but enzymatic activity of P3H1 is abolished. The protein retains the ability to form a complex with cartilage associated protein (CRTAP) and thus its collagen chaperone function, however. These mice have a normal appearance, have no growth defects, have normal cartilage plate histology, and normal cortical bone, but show decreased trabecular bone. This model recapitulates elements of the bone phenotype of OI, but not the cartilage and growth phenotypes caused by the loss of the prolyl 3-hydroxylation complex.

Development

An H662A (histidine to alanine; CAT to GCT; ENSEMBL 119247505-119247506) mutation was introduced to a catalytic site encoded by exon 14 via a recombineering strategy. A loxP-flanked neomycin resistance selection cassette was placed upstream, in intron 13. The mutation was created in AB2.2 129S7/SvEvBrd-Hprt1^b-m2-derived embryonic stem (ES) cells. The neomycin cassette was excised from resultant mice through crosses with a germline Cre strain on a C57BL/6 background. This strain was maintained on a mixed C57BL/6-129S genetic background by the donating laboratory.

Allele

Symbol: P3h1^tm1.1Brle
Name: targeted mutation 1.1, Brendan Lee
MGI accession ID: MGI:5532323
Generation method: Targeted
Attributes: Hypomorph
Marker symbol: P3h1
Marker name: prolyl 3-hydroxylase 1
Chromosome: 4
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: An H662A (histidine to alanine; CAT to GCT) mutation was introduced to a catalytic site encoded by exon 14 via a recombineering strategy. A loxP-flanked neomycin resistance selection cassette was placed upstream, in intron 13. Germ line, cre-mediated recombination removed the neomycin cassette. Please note that an error in the publication indicates that the mutation was introduced into exon 12, the correct exon is 14.