The colony at The Jackson Laboratory Repository is on a mixed 129S genetic background and may not recapitulate the phenotype originally described.
The following text reflects the phenotype reported by the donating investigator (Dr. Iris Lindberg) on a "129Sv" genetic background (probably "Taconic Sv129" (129S6/SvEvJ)).
While heterozygotes are viable and fertile, mice homozygous for this mutation (7B2-null) die in prepubertal or pubertal ages (5 weeks) with severe cardio-respiratory failure, convulsions, and hypothermia. No transcripts are detected in brain tissue from the targeted gene. 7B2-null mice are unable to make an active form of prohormone convertase 2 (PC2) and have high circulating corticosterone. Homozygotes on the "129Sv" genetic background exhibit Cushing's-like disease pathologies of liver, pancreas, and pituitary; including pituitary-dependent hyperadrenocorticosteronism, severe hypoglycemia, hyperproinsulinemia, adrenal hypertrophy, pituitary hypotrophy, and altered islet cell morphology. 7B2-null mice develop the disease from intermediate lobe ACTH hypersecretion (rather than from pituitary adenomas). Other abnormalities include thinning fur, thin tail, skeletal defects, dorsal and intraperitoneal adipose deposits, low blood sugar, fatty liver, and inability to synthesize glucagon. The donating investigator reports that null pups on the 129/SvEv genetic background are distinguishable by appearance, do not compete well for milk, and suggests thinning litters to 1-2 mice to obtain homozygotes.
In 2008, 7B2-null mice on the mixed 129S genetic background were sent from The Jackson Laboratory Repository colony back to the donating investigator (Dr. Iris Lindberg; now at University of Maryland). In November 2010, Dr. Lindberg reported that 7B2-null mice no longer exhibit the lethal phenotype observed for 7B2-null mice on a "129Sv" genetic background (probably "Taconic Sv129" (129S6/SvEvJ)). The cause of this is not known; but may be due to 129 substrain differences and/or husbandry changes in different vivaria, or other. In addition, Dr. Lindberg backcrossed the mice onto "the Taconic 129Sv background" for eight generations and was unable to recapitulate the homozygous lethal phenotype. Therefore, the 7B2-null mice on the mixed 129S genetic background distributed from The Jackson Laboratory Repository may no longer represent a Cushing's disease model.
These 7B2-null mice may be useful in studies of corticosterone excess and its profound developmental effects, Cushing's disease, and other neuro-endocrine, obesity, or metabolism research. However, it should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
