B6.129P2-Slc30a7^Gt(XC827)Byg/J

Stock number: 039235
Product name: Znt7 KO
Research areas: Cancer Research, Cell Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research

Description

Znt7 knock-out (KO) mice have a gene trap vector, containing a β-galactosidase-neomycin (β-geo) gene, inserted into intron 6 of the solute carrier family 30 (zinc transporter), member 7 (Slc30a7) gene. This insertion results in deletion of exon 7, intron 7 and portion of exon 8. This strain may be useful for studying zinc homeostasis and absorption.

Detailed description

Zinc transporter (ZNT) proteins mobilize cytosolic zinc to the extracellular space and to intracellular compartments and are essential for multiple physiological processes, such as regulation of the early secretory pathway, that plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of proteins. Therefore, any disturbance in zinc homeostasis can result in diseases such as cancer, neuronal degeneration, chronic inflammation, hypertension, osteoarthritis, and others. Mouse Znt7 protein, which is coded by solute carrier family 30 (zinc transporter), member 7 (Slc30a7), is localized to the Golgi apparatus in Znt-expressing cells. Znt7 expression is ubiquitous in mouse and human tissues with more abundant expression detected in the lung, small intestine, and prostate. These Znt7 knock-out (KO) mice harbor a gene-trap mutation, containing a β-galactosidase-neomycin (β-geo) fusion gene, which was inserted into intron 6 of the Slc30a7. This mutation resulted in deletion of exon 7, intron 7 and a portion of exon 8, leading to production of a truncated non-functional Znt7 protein.

Homozygous Znt7 KO mice are viable and fertile; however, the donating laboratory does indicate that homozygous breeding units produce smaller litter sizes (~4 pups/litter). Both homozygous males and homozygous females demonstrate lower fat mass and overall body weight compared to wildtype controls, but this phenotype was most significant in male homozygous mice. Zinc absorption was also significantly reduced in homozygous small intestine, liver, and kidney tissues compared to wildtype controls. These Znt7 KO mice may be useful for studying zinc metabolism and absorption as well as type 2 diabetes, cancer metastasis, and bone marrow development.

Development

The Znt7 knock-out (KO) allele was generated by inserting a gene trap vector (pGT1Lxf) containing the β-galactosidase/neo (β-geo) fusion protein into intron 6 of the endogenous solute carrier family 30 (zinc transporter), member 7 (Slc30a7) gene. This insertion resulted in deletion of exon 7, intron 7 and a portion of exon 8 and produces a truncated protein at amino acid 221. The target construct also contained mouse engrailed 2 (En2) gene sequence and a simian virus 40 polyadenylation signal (SV40pA). The construct was electroporated into 129P2/OlaHsd derived embryonic stem (ES) cells; this ES cell line (XC827) was obtained from the BayGenomics gene-trap resource and injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice to establish germline transmission and progeny were continually backcrossed to C57BL/6J mice for at least 10 generations using a marker-assisted speed congenic approach by the donating laboratory. After the line was established, these Znt7 KO mice were backcrossed to female C57BL/6J mice approximately every 2 years. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Slc30a7^Gt(XC827)Byg
Name: gene trap XC827, BayGenomics
MGI accession ID: MGI:3528432
Generation method: Gene trapped
Attributes: Null/Knockout
Synonyms: Znt7^-
Marker symbol: Slc30a7
Marker name: solute carrier family 30 (zinc transporter), member 7
Marker synonyms: 1810059J10Rik; 2610034N15Rik; 4833428C12Rik; ZHS; ZnT7; ZnT-7; ZnTL2
Chromosome: 3
Strain of origin: 129P2/OlaHsd
Molecular note: A beta-geo trap vector inserted into intron 6 of the gene and deleted exon 7, intron 7 and a portion of exon 8. The deletion is predicted to truncate the protein at amino acid 221, which is upstream of two potential transmembrane domains predicted to be necessary for protein function. Only expression of mutant transcript was detected by Northern blots of RNA from the small intestine of homozygotes.