BALB/c-Hdc^em1Huhu/J

Stock number: 037608
Product name: Hdc^GCbox-, Hdc^GC-
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

Hdc^GCbox mice carry a CRISPR/Cas9-generated deletion of noncoding Hdc (histamine decarboxylase) GC box sequences that possess enhancer activity. Mast cells, basophils, brain cells, and stomach cells from GC box-deficient mice transcribe the Hdc gene much less than similar cells from wildtype mice. Homozygotes fail to develop anaphylaxis following administration of IgE anti-TNP (trinitrophenyl) antibody.

Detailed description

Histamine is a critical mediator of anaphylaxis, a neurotransmitter, and a regulator of gastric acid secretion. Histidine decarboxylase (encoded by Hdc) is a rate-limiting enzyme for histamine synthesis.

Hdc^GCbox mice carry a CRISPR/Cas9-generated deletion of noncoding Hdc GC box sequences that possess enhancer activity. Homozygotes tend to have slightly reduced numbers of peritoneal mast cells. Hdc mRNA expression is considerably and significantly reduced in both bone marrow mononuclear cells (BMMCs) (90% reduction) and basophils (77% reduction). Hdc mRNA is significantly decreased in brain cells (83% reduction) and stomach cells (84% reduction), as well. Histamine contents in BMMCs and peritoneal mast cells derived from the homozygous mice are dramatically decreased (91% and 97% reduction, respectively).

Homozyous mutant mice develop little or no passive systemic anaphylaxis and release little histamine after the injection of IgE anti-TNP (trinitrophenyl) antibody and challenge with TNP-BSA (95% reduction in histamine release relative to wildtype mice).

Development

Sequences incorporating the GC box sequence (GGGCGG) of the mouse Hdc gene were deleted using CRISPR/cas9 methodologies. An sgRNA (TTTATGGGGGCGGGGC) was injected into BALB/cByJ zygotes. Resultant mice were backcrossed to BALB/c for 1 generations by the donating laboratory to help remove any off-target mutations.

Upon arrival at The Jackson Laboratory, sperm was cryopreserved. Cryorecovery/live colony development will involve BALB/cByJ (Stock No. 001026). (August, 2022)

Allele

Symbol: Hdc^em1Huhu
Name: endonuclease-mediated mutation 1, Hua Huang
MGI accession ID: MGI:7330187
Generation method: Endonuclease-mediated
Attributes: Not Applicable
Marker symbol: Hdc
Marker name: histidine decarboxylase
Chromosome: 2
Strain of origin: BALB/c
Molecular note: CRISPR/cas9 genome editing is used to delete sequences incorporating the noncoding GC box sequence (GGGCGG). The GC box sequences possess enhancer activity. mRNA expression is reduced in mast cells, basophils, brain cells, and stomach cells.