B6.Cg-Pds5b^{Tg(Wap-ERBB2)229Wzw}/J

Stock number: 010562
Research areas: Cancer Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

This transgenic line expresses the human ERBB2 (HER2) gene in mammary gland and brain, displays tolerance to ERBB2 antigen and may be useful in testing ERBB2-based vaccines and immunotherapies.

Detailed description

Mice that are hemizygous for the transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These transgenic mice express human ERBB2 (HER2) under the control of the mouse whey acid protein promoter (Wap). The Wap promoter directs expression to the mammary gland and molecular layer of the cerebellum. Mice do not develop spontaneous tumors, but are tolerant to ERBB2 tumor associated antigen, developing tumors after inoculation with ERBB2 expressing tumor cells. Anti-tumor immunity can be induced using aggressive DNA vaccination. This mutant mouse strain may be useful in testing ERBB2-based vaccines and immunotherapies.

Sequencing has identified the transgene integration site as intron 2 of the Pds5b gene (PDS5 cohesin associated factor B) on chromosome 5. The 162 copy (approx 1.1 Mb) integration disrupts Pds5b rendering it a null allele. Embryos homozygous for the mutation are severely underdeveloped with jaundice and disruptions to limb and facial formation by E14-15, no embryos survive to birth.

Development

A transgenic construct containing a mouse 2.6 kb whey acidic protein (Wap) promoter fused to a human ERBB2 4.4 kb cDNA followed by the bovine growth hormone polyadenylation signal. Transgenic mice were generated by microinjection into (C57BL/6 x C3H) F1 mouse embryos. This line has been backcrossed to C57BL/6 for more than 25 generations by the donating investigator.

As reported by Yong CSM et al (PLoS One 2015; 10(9):e0136817), the transgene inserted as a 162 bp concatemer (approx. 1.1 Mb) 19 nucleotides upstream of exon 3 of the Pds5b gene on Chr 5. The insertion disrupts Pds5b resulting in a null allele.

Allele

Symbol: Pds5b^{Tg(Wap-ERBB2)229Wzw}
Name: transgene insertion 229, Wei-Zen Wei
MGI accession ID: MGI:3850477
Generation method: Transgenic
Attributes: Null/Knockout; Inserted expressed sequence; Humanized sequence
Marker symbol: Pds5b
Marker name: PDS5 cohesin associated factor B
Chromosome: 5
Strain of origin: (C57BL/6 x C3H)F1
Expressed genes: ERBB2,erb-b2 receptor tyrosine kinase 2,human
Molecular note: A transgenic construct containing a mouse 2.6 kb whey acidic protein (Wap) promoter fused to a human ERBB2 4.4 kb cDNA followed by the bovine growth hormone polyadenylation signal. Line 229 inserted into intron 2 (19 bp upstream of exon 3).