C3.Cg-Prkdc^scid Tg(Mt1-HGF)1Gvw/GvwJ

Stock number: 030205
Product name: hHGF-Tg SCID , hHGF^tg-SCID , C3HSCIDhHGF
Research areas: Cancer Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

hHGF-Tg SCID mice (also called hHGF^tg-SCID or C3HSCIDhHGF) allow enhanced growth of heterotopic MET-expressing human tumor xenografts - including those derived from lung, breast, kidney, colon, stomach and pancreas. These mice may be useful in studying the HGF/MET pathway in human tumor xenografts and mouse tumor allografts.

Detailed description

hHGF-Tg SCID mice are C3H-congenic animals homozygous for the severe combined immunodeficiency spontaneous mutation (Prkdc^scid; commonly referred to as scid) and hemizygous for the hHGF-Tg transgene (Tg(Mt1-HGF)#Gvw; mouse metallothionein I promoter driving expression of human hepatocyte growth factor [hHGF/SF]).

hHGF-Tg SCID mice exhibit elevated serum hHGF titer and enlarged liver. Overall, mice homozygous for scid exhibit T- and B-cell deficiency, lymphopenia, hypogammaglobulinemia and a normal hematopoietic microenvironment (see additional phenotype description for C3H-congenic scid mice; Stock No. 001131). Presence of the hHGF-Tg transgene also results in black pigmentation in tail, ears, paws and nose (allowing them to be easily distinguished from non-transgenic littermates).

While human HGF activates both the human and murine form of its tyrosine kinase receptor (met proto-oncogene [MET; c-Met]), the endogenous murine HGF is unable to activate human MET. hHGF-Tg SCID mice have ectopic expression of hHGF that (in combination with scid) enhances the growth of heterotopic MET+ human tumor xenografts - including those derived from lung, breast, kidney, colon, stomach and pancreas. Importantly, the donating investigator reports that these xenograft results are from mice maintained on normal diet, and no significant differences in transgene expression levels are observed following dietary zinc supplementation.

The donating investigator reports that hHGF-Tg SCID males are viable and fertile, but females hemizygous for Tg(Mt1-HGF)#Gvw are infertile (regardless of scid genotype).

hHGF-Tg SCID mice are immunodeficient. As such, and similar to other immunodeficient strains, maintenance in high health status (specific pathogen-free) vivaria promotes overall colony health. If hHGF-Tg SCID animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.

Development

hHGF-Tg SCID mice (also called hHGF^tg-SCID or C3HSCIDhHGF) have the severe combined immunodeficiency spontaneous mutation (Prkdc^scid) and the Tg(Mt1-HGF)#Gvw transgene (hHGF-Tg). Each is described in more detail below.

The Prkdc^scid mutation (commonly referred to as scid) occurred spontaneously in a colony of BALB/c-Igh^b (C.B-17) mice maintained at the Institute for Cancer Research in Philadelphia, PA. The mutation was backcrossed onto the C3H/HeSn genetic background for ten or more generations to establish the C3H-congenic scid mouse strain (C3H.scid; C3SnSmn.CB17-Prkdc^scid/J; Stock No. 001131). Before 2005, Dr. George F. Vande Woude (Van Andel Institute) obtained C3H.scid mice from The Jackson Laboratory and used them for creating the hHGF-Tg SCID mouse line (Stock No. 030205).

The hHGF-Tg transgene was created in the laboratory of by Dr. George F. Vande Woude (Van Andel Institute) to have the mouse metallothionein I promoter sequences (Mt1) upstream of a cDNA sequence encoding the human hepatocyte growth factor (HGF; hHGF/SF). The transgene was microinjected into C3H/B6 mouse embryos. Founders were identified by genotype, and individual founder lines were backcrossed seven generations onto C57BL/6J. No specific founder line # was identified. Next, the hhHGF-Tg mice were backcrossed at least ten generations to C3H.scid (originally obtained from Stock No. 001131). The resulting C3H-congenic scid hHGF-Tg colony (hHGF-Tg SCID) was routinely maintained by breeding C3H.scid homozygous females with hHGF-Tg SCID males (homozygous for scid and hemizygous for hHGF-Tg). In 2017, hHGF-Tg SCID males with agouti coat color were sent to The Jackson Laboratory Repository. Upon arrival, sperm was cryopreserved. To establish our living colony, an aliquot of the frozen sperm was used to fertilize oocytes from C3H-congenic scid females (Stock No. 001131).
Of note, it is not known if the Y chromosome has been fixed to the C57BL/6J or C3H genetic background.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Synonyms: scid
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Marker synonyms: DNAPDcs; DNAPK; DNA-PK; DNAPKc; DNA-PKC; DNA-PKcs; DNPK1; DOXNPH; dxnph; HYRC; HYRC1; IMD26; p350; S473K; slip; XRCC7
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: Tg(Mt1-HGF)1Gvw
Name: transgene insertion 1, George F Vande Woude
MGI accession ID: MGI:5829717
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: hHGF-Tg
Marker symbol: Tg(Mt1-HGF)1Gvw
Marker name: transgene insertion 1, George F Vande Woude
Chromosome: UN
Strain of origin: C3H or C57BL/6
Expressed genes: HGF,hepatocyte growth factor,human
Molecular note: The transgenic construct consists of mouse metallothionein I promoter sequences (Mt1) placed upstream of a cDNA sequence encoding the human hepatocyte growth factor.