B6.129S1-Gnai2^tm1.1Rneu/J

Stock number: 012768
Research areas: Cardiovascular Research, Developmental Biology Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Neurobiology Research

Description

A G184S point mutation was created in the Gnai2 (guanine nucleotide binding protein (G protein), alpha inhibiting 2; also called Gαi2) gene. A complex phenotype affecting multiple organ systems (heart, myeloid, skeletal, and central nervous system) can be observed. This strain may be useful in studies of signal transduction, pharmacology, diabetes, epilepsy, thrombosis, cardiology, and developmental biology.

Detailed description

A G184S point mutation was created in the Gnai2 (guanine nucleotide binding protein (G protein), alpha inhibiting 2; also called Gαi2) gene which disrupts interactions with regulator of G protein signaling (RGS) proteins that normally deactivate Gα G protein signals. A complex phenotype affecting multiple organ systems (heart, myeloid, skeletal, and central nervous system) can be observed. Homozygous mice and their cardiocytes exhibit enhanced muscarinic (M₂) but not adenosine (A₁) receptor-mediated responses. Isoproterenol-stimulated beating rates of heterozygous and homozygous hearts are significantly more sensitive to inhibition to carbachol than are those of wildtype mice.

Homozygous mice show slightly reduced adiposity. Unlike females, males placed on a high-fat diet are resistant to weight gain and have decreased body fat as compared to wildtype mice. Both males and females exhibit enhanced insulin sensitivity (protected from insulin resistance) and increased glucose tolerance.

Although fertile, both homozygotes and heterozygotes demonstrate reduced viability and decreased body weight. Homozygotes are born in low numbers for unknown reasons. Shortened long bones, growth retardation, enlarged spleen, elevated neutrophil and monocyte counts, enlarged heart, and behavioral hyperactivity are also observed primarily in homozygotes. This strain may be useful in studies of signal transduction, pharmacology, diabetes, epilepsy, thrombosis, cardiology, and developmental biology.

Development

A G184S mutation was introduced to exon 5 and a loxP-flanked neomycin cassette was placed in intron 5 of the targeted gene using 129S1/Sv-Oca2^pTyr⁺Kitl ⁺-derived CJ7 embryonic stem (ES) cells. The floxed neomycin cassette was excised in resultant mice by crossing them with Zp3-cre mice on a C57BL/6 background (see Stock No. 003651). The strain was backcrossed to C57BL/6 for 15 generations by the donating laboratory.

Allele

Symbol: Gnai2^tm1.1Rneu
Name: targeted mutation 1.1, Richard R Neubig
MGI accession ID: MGI:3711989
Generation method: Targeted
Attributes: Not Applicable
Synonyms: Galphai2^G184S; Galphai2^GS
Marker symbol: Gnai2
Marker name: guanine nucleotide binding protein (G protein), alpha inhibiting 2
Marker synonyms: Galphai2; Gia; GIP; Gnai-2; GNAI2B; H_LUCA15.1; H_LUCA16.1; Hg1c
Chromosome: 9
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: Cre mediated recombination resulted in the loss of the floxed neo from Gnai2^tm1Rneu, leaving a glycine to serine substitution G184S in exon 5.