Reference SummaryYu R, Endocrinol Nutr 2012 Nov;59(9):523-30
Title |
Glucagon receptor is required for long-term survival: a natural history study of the Mahvash disease in a murine model. |
Authors |
Yu R; Ren SG; Mirocha J |
Journal |
Endocrinol Nutr |
Volume |
59 |
Issue |
9 |
Year |
2012 |
Pages |
523-30 |
Abstract |
BACKGROUND AND AIM: We have described a novel Mahvash disease of hyperglucagonemia and pancreatic neuroendocrine tumors (PNETs) associated with an inactivating glucagon receptor mutation, and identified the glucagon receptor-deficient (Gcgr(-/-)) mice as its murine model. We aim to elucidate the natural history of the rare Mahvash disease by long-term observation of the Gcgr(-/-) mice. MATERIALS AND METHOD: Wild type (WT) (n=52), heterozygous (n=127), and Gcgr(-/-) (n=56) mice living under standard vivarium conditions were observed without specific treatments over 22 months. Autopsy was performed on dead animals. RESULTS: The WT and heterozygous mice did not exhibit any measurable differences. The Gcgr(-/-) mice became progressively lethargic and cachexic after 12 months. Random glucose levels were stable in WT and heterozygous mice but decreased with age in the Gcgr(-/-) mice. At the end of observation, 28/56 Gcgr(-/-), 7/52 WT, and 24/127 heterozygous mice died. The survival curve of Gcgr(-/-) mice began to separate from those of WT and heterozygous mice at 12 months and the survival difference widened with age. At 18 months, survival probability was 17% for Gcgr(-/-) mice but 77% for WT and 81% for heterozygous mice. Autopsy revealed numerous PNETs up to 15 mm in diameter in most well-preserved Gcgr(-/-) pancreata (17/20) but none in WT or heterozygous ones. Four Gcgr(-/-) mice developed liver or subcutaneous metastasis. CONCLUSION: The untreated Mahvash disease may cause cachexia, severe hypoglycemia, and early death. Patients with Mahvash disease need to undergo life-long surveillance for PNETs. Functional glucagon receptor is thus required for long-term survival. |
Links |
J:305077 – MGI References 22951296 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| DBA/1LacJ | Adrenal gland tumor | Adrenal gland |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | Adrenal gland tumor | Adrenal gland |
0.79 |
||
| DBA/1LacJ-Gcgrtm1Jcp | Adrenal gland tumor | Adrenal gland |
0 |
||
| CE/WyDi | Pancreas - Islet of Langerhans - Alpha cell glucagonoma | Pancreas - Islet of Langerhans - Alpha cell |
observed |
||
| DBA/1LacJ | Pancreas - Islet of Langerhans dysplasia | Pancreas - Islet of Langerhans |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | Pancreas - Islet of Langerhans dysplasia | Pancreas - Islet of Langerhans |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp | Pancreas - Islet of Langerhans dysplasia | Pancreas - Islet of Langerhans |
observed |
||
| DBA/1LacJ-Gcgrtm1Jcp | Pancreas adenoma | Pancreas |
observed |
||
| CE/WyDi | Pancreas insulinoma | Pancreas |
observed |
||
| DBA/1LacJ | Pancreas lesion | Pancreas |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | Pancreas lesion | Pancreas |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp | Pancreas lesion | Pancreas |
30.36 |
||
| DBA/1LacJ-Gcgrtm1Jcp | Pancreas tumor | Pancreas |
observed - 100 |
||
| DBA/1LacJ | Pancreas tumor | Pancreas |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | Pancreas tumor | Pancreas |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp | Pancreas tumor - endocrine | Pancreas |
10 |
||
| DBA/1LacJ | Pancreas tumor - endocrine | Pancreas |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | Pancreas tumor - endocrine | Pancreas |
0 - observed |
||
| CE/WyDi | Pancreas tumor - mixed | Pancreas |
observed |
||
| DBA/1LacJ | Pancreas tumor - neuroendocrine | Pancreas |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | Pancreas tumor - neuroendocrine | Pancreas |
0 |
||
| DBA/1LacJ-Gcgrtm1Jcp | Pancreas tumor - neuroendocrine | Pancreas |
30.36 |
||
| DBA/1LacJ | Pelvis tumor | Pelvis |
1.92 |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | Pelvis tumor | Pelvis |
1.57 |
||
| DBA/1LacJ-Gcgrtm1Jcp | Pelvis tumor | Pelvis |
0 |
||
| DBA/1LacJ | (Unspecified organ) lesion - benign | (Unspecified organ) |
0 - observed |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | (Unspecified organ) lesion - benign | (Unspecified organ) |
0 - observed |
||
| DBA/1LacJ-Gcgrtm1Jcp | (Unspecified organ) lesion - benign | (Unspecified organ) |
0 - observed |
||
| DBA/1LacJ | (Unspecified organ) tumor | (Unspecified organ) |
1.92 |
||
| DBA/1LacJ-Gcgrtm1Jcp/+ | (Unspecified organ) tumor | (Unspecified organ) |
2.36 |
||
| DBA/1LacJ-Gcgrtm1Jcp | (Unspecified organ) tumor | (Unspecified organ) |
30.36 |