B6.Cg-Tg(Syn1-ACE2)10Sig/LazarJ

Stock number: 034899
Product name: SA line 10 , Syn-hACE2 line 10
Research areas: Neurobiology Research, Research Tools

Description

Syn-hACE2 transgenic mice express human ACE2 in the brain using the neuron specific rat synapsin 1 promoter. Human ACE2 is the receptor used for cellular entry by several coronaviruses, including severe acute respiratory syndrome coronavirus-1 (SARS-CoV) and -2 (SARS-CoV-2). These mice may be useful for studying antiviral therapies to coronavirus and the disease outbreak COVID-19.

Detailed description

Syn-hACE2 transgenic mice express human ACE2 (angiotensin I converting enzyme (peptidyl-dipeptidase A) 2) under the control of the neuron specific rat synapsin (Syn1) promoter. ACE2 encodes the proteins used by the severe acute respiratory syndrome coronavirus (SARS-CoV) to gain entry to cells. Specifically, these mice contain 0.5 kb of the Syn1 genomic sequence upstream of the human angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (hACE2) full open reading frame. Mice from founder line 10 have the highest level of transgene expression in the brain. No expression is found in other tissues tested. Expression is widespread in the central nervous system including cortex, hypothalamus, and brainstem. Mice hemizygous for the transgene are viable and fertile, the donating investigator has not attempted to produce homozygotes. Syn-hACE2 mice exhibit an attenuated development of neurogenic hypertension and heart failure when chronically infused with angiotensin-II (Feng et al. Circ Res. 2010; PMID:19926873) or subjected to coronary artery ligation, respectively (Xiao et al. Hypertension 2011; PMID:22025374). In addition, brain angiotensin II type 2 (Agtr2 or AT2)/AT1 and Mas/AT1 receptor ratios and nitric oxide levels are increased in comparison to controls.

Recent research indicates that this line may also be useful in studies related to the study of 2019 novel coronavirus (SARS-CoV-2) pathogenesis.

Development

The 4.4 kb syn-hACE2 transgene consists of a rat synapsin 1 promoter and a cDNA encoding the full open reading frame of the human angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (ACE2) followed by a polyA tail. The linearized construct was microinjected into fertilized (C57BL/6J x SJL/J)F2 oocytes at the University of Iowa Transgenic Animal Facilities for Dr. Curt Sigmund. Founder line 10, with the highest level of expression, was subsequently mated to C57BL/6J. Mice were transferred to Dr. Eric Lazartigues (Louisiana State University) and backcrossed for at least 25 generations to C57BL/6J (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 C57BL/6J oocytes.

In 2020, 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 males sent to The Jackson Laboratory Repository. Two of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Tg(Syn1-ACE2)10Sig
Name: transgene insertion 10, Curt Sigmund
MGI accession ID: MGI:6401191
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: syn-hACE2
Marker symbol: Tg(Syn1-ACE2)10Sig
Marker name: transgene insertion 10, Curt Sigmund
Chromosome: UN
Strain of origin: (C57BL/6J x SJL/J)F2
Site of expression: Expression is widespread in the central nervous system including cortex, hypothalamus, and brainstem