129S;B6-Del(3Bglap2-Bglap)2Kry/J

Stock number: 034070
Product name: Ocn^-
Research areas: Diabetes and Obesity Research, Endocrine Deficiency Research, Internal/Organ Research, Metabolism Research, Reproductive Biology Research

Description

A single mutational event was used to target two genes, Bglap1 and Bglap2. The osc^m1 construct containing the neomycin resistance gene deleted exon 4 of Bglap1 and the entire coding region of Bglap2 by homologous recombination. A third locus in this cluster, Bglap-rs1, was left intact. These mice may be useful for studying the role of osteocalcin in bone as an endocrine organ.

Detailed description

A single mutational event was used to target two genes, Bglap1 and Bglap2. The osc^m1 construct containing the neomycin resistance gene deleted exon 4 of Bglap1 and the entire coding region of Bglap2 by homologous recombination. A third locus in this cluster, Bglap-rs1, was left intact. These genes are also known as Osteocalcin genes 1 and 2 and are part of the mouse osteocalcin cluster which contains three genes: these two which encode osteocalcin and osteocalcin-related gene (ORG), which is expressed in kidney but not in bone. The Bglap coding sequences are 96% identical, and they are highly abundant bone proteins secreted by osteoblasts that regulates bone remodeling and energy metabolism. These knock-out mice exhibit high bone mass, reduced male fertility (but not female fertility), metabolic abnormalities including glucose intolerance and insulin resistance, muscle and adipose tissue abnormalities, and defect in cognition. Homozygous mice are viable and fertile, however the donating lab reports that homozygous males born from homozygous female mice will have reduced numbers of offspring.

Development

A single mutational event was used to target two genes, Bglap1 and Bglap2. The osc^m1 construct containing the neomycin resistance gene deleted exon 4 of Bglap1 and the entire coding region of Bglap2 by homologous recombination. A third locus in this cluster, Bglap-rs1, was left intact. The construct was electroporated into 129S7/SvEvBrd-Hprt^b-m2-derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. Offspring were bred to 129SvE/Tac for at least 7 generations by the donating lab (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize 129S1/SvImJ oocytes (Stock No. 002448).



In 2019 a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Three of the 43 markers on Chromosomes 17, 18, and 19 were segregating with 129, suggesting an incomplete backcross.