FVB-Tg(Ckm-IGF1R*K1003R)1Dlr/J

Stock number: 016618
Research areas: Cell Biology Research, Diabetes and Obesity Research

Description

MKR transgenic mice have the murine Ckm promoter directing expression of the human IGF-1R gene containing the K1003R mutation. These mice may be useful for studying insulin signaling and Type 2 Diabetes.

Detailed description

MKR transgenic mice have the murine creatine kinase, muscle (Ckm) promoter directing expression of the human insulin-like growth factor I receptor (IGF-1R) gene containing the K1003R mutation. Homozygous MKR mice are viable and fertile. IGF-1R is a tyrosine kinase transmembrane receptor dimer which mediated cell signaling through IGF binding and promotes cell survival and cell proliferation. The K1003R mutation inactivates the ATP binding site of the receptor. These transgenic mice have ~12 copies of the transgene, and exhibit a 10 fold increase in expression in skeletal muscle, with weak expression in cardiac muscle. Expression of the mutant receptor results in the formation of hybrid receptors with endogenous IGF-1R and insulin receptors, leading to a decrease in glucose uptake, insulin resistance, beta cell dysfunctions, and rapid development of diabetes. These mice exhibit 20% reduction in body weight during the first month of life, and continue to have a 10% reduction in body weight throughout life compared to wildtype. These mice may be useful for studying insulin signaling and Type 2 Diabetes.

Development

The MKR transgene was designed with the human insulin-like growth factor I receptor (IGF-1R) gene driven by a murine creatine kinase, muscle (Ckm) promoter. The point mutation K1003R was introduced, resulting in a dominant negative IGF-1R. The transgene was microinjected into fertilized FVB/N oocytes, and founder mice were bred to FVB/N mice. Upon arrival at The Jackson Laboratory, transgenic mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation.

Allele

Symbol: Tg(Ckm-IGF1R*K1003R)1Dlr
Name: transgene marker 1, Derek LeRoith
MGI accession ID: MGI:3842765
Generation method: Transgenic
Attributes: Dominant negative; Inserted expressed sequence; Humanized sequence
Synonyms: MCK-KR-hIGF-IR; MKR
Marker symbol: Tg(Ckm-IGF1R*K1003R)1Dlr
Marker name: transgene marker 1, Derek LeRoith
Marker synonyms: MCK-KR-hIGF-IR; MKR
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: IGF1R,insulin like growth factor 1 receptor,human
Molecular note: The promoter, enhancer 1, exon 1, first intron/enchancer 2, and first 16 base pairs of exon 2 were used to drive muscle-specific expression of a dominant-negative human gene with nucleotide substitutions that result in the amino acid substitution of arginine for lysine at position 1003 (K1003R). Five lines were created with around 12 copies of the transgene. No line names were given.