NOD.Cg-Prkdc^scid Il2rg^tm1Wjl Tg(SERPINA1*E342K)#Slcw/SzJ

Stock number: 028842
Product name: NSG-PiZ
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

NSG-PiZ mice express mutant human SERPINA1 (Glu342Lys mutation) on the immunodeficient NOD scid gamma (NSG) background, providing a stable engraftment environment for primary human hepatocytes after partial hepatectomy. This strain may be useful in studies utilizing a humanized liver xenograft mouse model.

Detailed description

NSG-PiZ mice do not express the Prkdc gene nor the X-linked Il2rg gene, but do express the mutant human SERPINA1 PiZ variant with a Glu342Lys point mutation. Female NSG-PiZ mice, homozygous for both alleles and the transgene, and male NSG-PiZ mice, homozygous for the Prkdc allele and transgene and hemizygous for the X linked Il2rg allele, are viable and fertile. After partial (two-thirds) hepatectomy, NSG-PiZ mice engrafted with primary human hepatocytes exhibit stable human albumin serum levels between 0.4 and 2.8 mg/ml.

Development

Transgenic Tg(SERPINA1*E342K)#Slcw mice on a segregating background were obtained by Dr. Leonard Shultz (The Jackson Laboratory) from Dr. David Perlmutter (University of Pittsburgh School of Medicine). The mice were crossed to NOD scid females (Stock No. 001303), and then backcrossed to NSG, NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ, (Stock No. 005557) mice using a marker assisted speed congenic protocol.

The Tg(SERPINA1*E342K)#Slcw transgenic construct containing the entire PiZ variant of the human SERPINA1, serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1, gene was injected into fertilized (ICR x C57BL/6)F1 mouse eggs. The mice may have been crossed to FVB/N.

NSG double mutant mice were produced by breeding female NOD.CB17-Prkdc^scid/J (Stock No. 001303) mice with male mice bearing the X-linked B6.129S4-Il2rg^tm1Wjl/J allele (Stock No. 003174). The resulting male mice heterozygous for the Prkdc^scid allele and hemizygous for the Il2rg^tm1Wjl allele were crossed to female NOD.CB17-Prkdc^scid/J (Stock No. 001303) mice for eight generations. Heterozygotes were interbred to produce mice homozygous for the Prkdc^scid allele and homozygous (females) or hemizygous (males) for the Il2rg^tm1Wjl allele.

Allele

Symbol: Tg(SERPINA1*E342K)#Slcw
Name: transgene insertion, Savio L C Woo
MGI accession ID: MGI:3847801
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SERPINA1*E342K)#Slcw
Marker name: transgene insertion, Savio L C Woo
Chromosome: UN
Strain of origin: (ICR x C57BL/6)F1
Expressed genes: SERPINA1,serpin family A member 1,human
Molecular note: The transgene construct contains the entire human alpha₁-antitrypsin (AAT or SERPINA1) gene encoding the Z variant allele which has a Glu->Lys substitution at position 342, plus 2.0 and 2.3 kb of 5' and 3' genomic sequences, respectively.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Chromosome: 16
Strain of origin: C.BKa-Igh^b/Icr
Site of expression: T and B lymphocytes.
Molecular note: A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*).

Allele

Symbol: Il2rg^tm1Wjl
Name: targeted mutation 1, Warren J Leonard
MGI accession ID: MGI:1857455
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
Chromosome: X
Strain of origin: 129S4/SvJae
Site of expression: Primarily lymphoid cells.
Molecular note: A neomycin resistance cassette replaced part of exon 3 and all of exons 4 - 8 of the gene, resulting in the loss of most of the extracellular domain and all of the transmembrane and cytoplasmic domains of the protein.