C.FVB-Tg(ICAM1)4Grom/J

Stock number: 025699
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools, Virology Research

Description

hICAM-1 tg line 4 mice express the human intercellular adhesion molecule 1. hICAM-1 tg line 4 mice are a model for the common cold following CAV21 Coxsackievirus A21 (CAV21) infection. These mice may also be useful for studying other viruses that use ICAM-1 to invade cells and cause disease, such as provocation poliomyelitis and HIV.

Detailed description

BALB.hICAM-1 tg line 4 mice express the human intercellular adhesion molecule 1. The donating investigator reports that mice homozygous for the hICAM-1 transgene are viable and fertile with no spontaneous observed abnormalities and no breeding difficulties.
The common-cold-causing coxsackievirus A21 (CAV21) is an enterovirus with tropism for the human intercellular adhesion molecule 1 (hICAM-1). Because cells from BALB.hICAM-1 tg line 4 mice support CAV21 replication, the protein expressed from the transgene (hICAM-1) is functional and able to confer virus susceptibility to mouse cells. For BALB.hICAM-1 tg line 4 mice, the hICAM-1 expression levels and tissue distribution are similar to those reported for human (including on the apical surface of respiratory tract epithelial cells). Specifically, hICAM-1 expression is highest in lung and spleen, low to absent in liver, ileum, kidney and heart, and undetectable in brain.
Following intratracheal injection of CAV21, BALB.hICAM-1 tg line 4 mice exhibit rapid clearance of the inoculum in respiratory tract. Therefore, serial passage of CAV21 in hICAM-1 tg mouse lungs allows for the selection for respiratory tract-competent CAV21 variants of the common-cold-causing coxsackievirus A21.
Following intramuscular injection of CAV21, BALB.hICAM-1 tg line 4 mice develop a paralytic condition consistent with provocation poliomyelitis; that is, enhanced susceptibility to neurological complications and localization of initial paresis to the injected limb via retrograde axonal transport.

Development

The human ICAM1 transgene (HsICAM-1 or hICAM-1) was created by Dr. Matthias Gromeier (Duke University Medical Center) by first obtaining the bacterial artificial chromosome (BAC) CTD-2369P2 (California Institute of Technology Human BAC Library D; GenBank accession no. AC011511). A ~39 kbp segment was isolated with entire human intercellular adhesion molecule 1 gene (ICAM1), including ~18.9 kbp upstream and ~4.6 kbp downstream of ICAM1. The transgene was injected into the pronuclei of FVB/NHsd fertilized mouse oocytes. Founder animals were bred to wildtype BALB/cAnNTac mice to establish founder lines. Because founder line 4 was determined to have hICAM-1 expression intensity and tissue distribution similar to human, mice from line 4 were chosen to characterize the behavior of transgenic animals. Founder line 4 mice were backcrossed to wildtype BALB/cAnNTac mice for 27 generations by the donating lab (see SNP note below). The resulting BALB.hICAM-1 tg line 4 mice (or BALB.HsICAM-1 tg line 4) were then bred together to make homozygous. Sperm from homozygous males was frozen, and the frozen sperm was sent to The Jackson Laboratory in 2014. To establish our living colony, an aliquot of the frozen sperm was used to fertilize oocytes from BALB/cByJ inbred females (Stock No. 001026). The donating investigator reports that, at least once during backcrossing, a heterozygous female was bred to a BALB/cAnNTac inbred male (thus the Y chromosome of the congenic strain is of BALB/c origin).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 3 markers that distinguish between BALB substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 27 markers throughout the genome suggested an FVB genetic background, and all 3 markers that determine BALB were found to be segregating.

Allele

Symbol: Tg(ICAM1)4Grom
Name: transgene insertion 4, Matthias Gromeier
MGI accession ID: MGI:5604232
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(ICAM1)4Grom
Marker name: transgene insertion 4, Matthias Gromeier
Chromosome: UN
Strain of origin: FVB/NHsd
Expressed genes: ICAM1,intercellular adhesion molecule 1,human
Site of expression: ICAM1 expression is highest in lung and spleen, low to absent in liver, ileum, kidney and heart, and undetectable in brain.
Molecular note: A ~39 kbp segment was isolated from BAC CTD-2369P2 containing the entire human intercellular adhesion molecule 1 gene (ICAM1), including ~18.9 kbp upstream and ~4.6 kbp downstream. Five founder lines were generated and founder line 4 was determined to have hICAM-1 expression intensity and tissue distribution similar to human.