B6;129S7-Glg1^tm1Brle/J

Stock number: 021770
Research areas: Developmental Biology Research, Internal/Organ Research

Description

These mice carry a knockout allele of Glg1 (golgi apparatus protein 1; also known as E-selectin ligand 1) which may be useful in studies of skeletal growth and homeostasis.

Detailed description

The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. Glg1 (golgi apparatus protein 1; also known as E-selectin ligand 1) regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature transforming growth factor beta (TGFB).

These mice carry a knockout allele of Glg1 which involves a deletion of exons 13-16. Homozygous embryos and neonates (E14.5, E17.5, P3, and P7) are smaller than wildtype littermates. At birth, heterozygotes appear normal, but homozygous knockout pups are approximately 30%-50% smaller and show a higher rate of perinatal lethality.

Skeletal preparations of homozygotes show generalized shortening and thinning of all bony elements and distinctively narrow rib cages. A shortening of growth plates affecting both the proliferating zone (PZ) and the hypertrophic zone (HZ) involves decreased chondrocyte cell density and proliferation as well as increased extracellular matrix deposition. This is accompanied by increased mature TGFB2 and phosphorylated SMAD2 in the cartilage.

Development

Exons 13-16 were replaced with a puromycin resistance cassette and 3' Hprt minigene in the AB2.2 129S7/SvEvBrd-Hprt1⁺-derived embryonic stem (ES) cell line. Resultant chimeric males were mated with C57BL/6J females. This strain was maintained on a mixed C57BL6 and 129 genetic background by the donating laboratory.

Allele

Symbol: Glg1^tm1Brle
Name: targeted mutation 1, Brendan Lee
MGI accession ID: MGI:4829764
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Glg1
Marker name: golgi apparatus protein 1
Chromosome: 8
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: Exons 13 through 16 were replaced with a puro cassette and 3' Hprt minigene. The absence of protein expression was confirmed by western blot on brain extracts.