ArticleThe Journal of endocrinology2010
A novel spontaneous mutation of Irs1 in mice results in hyperinsulinemia, reduced growth, low bone mass and impaired adipogenesis.
Article in The Journal of endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
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- Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway.Scientific reports · 2025Article
- Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARActa pharmaceutica Sinica. B · 2023Article
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- Hearing impairment due toDisease models & mechanisms · 2020Article
- Potential applications for rhIGF-I: Bone disease and IGFI.Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2020Review
- Gene expression profile during proliferation and differentiation of rainbow trout adipocyte precursor cells.BMC genomics · 2017Article
- Bone Cell Bioenergetics and Skeletal Energy Homeostasis.Physiological reviews · 2017Review
- IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Leaf Extract from Lithocarpus polystachyus Rehd. Promote Glycogen Synthesis in T2DM Mice.PloS one · 2016Article
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- Igfbp2 Deletion in Ovariectomized Mice Enhances Energy Expenditure but Accelerates Bone Loss.Endocrinology · 2015Article
- Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ mouse.Endocrinology · 2014Article
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- Marrow fat and bone--new perspectives.The Journal of clinical endocrinology and metabolism · 2013Review
- Insulin-like growth factor 1 physiology: lessons from mouse models.Endocrinology and metabolism clinics of North America · 2012Review
- A specific role for phosphoinositide 3-kinase and AKT in osteoblasts?Frontiers in endocrinology · 2012Article
- Mitogen-activated protein kinase phosphatase 1 regulates bone mass, osteoblast gene expression, and responsiveness to parathyroid hormone.The Journal of endocrinology · 2011Article
- The Sweet Pee model for Sglt2 mutation.Journal of the American Society of Nephrology : JASN · 2011Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
A spontaneous mouse mutant, designated 'small' (sml), was recognized by reduced body size suggesting a defect in the IGF1/GH axis. The mutation was mapped to the chromosome 1 region containing Irs1, a viable candidate gene whose sequence revealed a single nucleotide deletion resulting in a premature stop codon. Despite normal mRNA levels in mutant and control littermate livers, western blot analysis revealed no detectable protein in mutant liver lysates. When compared with the control littermates, Irs1(sml)/Irs1(sml) (Irs1(sml/sml)) mice were small, lean, hearing impaired; had 20% less serum IGF1; were hyperinsulinemic; and were mildly insulin resistant. Irs1(sml/sml) mice had low bone mineral density, reduced trabecular and cortical thicknesses, and low bone formation rates, while osteoblast and osteoclast numbers were increased in the females but not different in the males compared with the Irs1(+/+) controls. In vitro, Irs1(sml/sml) bone marrow stromal cell cultures showed decreased alkaline phosphatase-positive colony forming units (pre-osteoblasts; CFU-AP+) and normal numbers of tartrate-resistant acid phosphatase-positive osteoclasts. Irs1(sml/sml) stromal cells treated with IGF1 exhibited a 50% decrease in AKT phosphorylation, indicative of defective downstream signaling. Similarities between engineered knockouts and the spontaneous mutation of Irs1(sml) were identified as well as significant differences with respect to heterozygosity and gender. In sum, we have identified a spontaneous mutation in the Irs1 gene associated with a major skeletal phenotype. Changes in the heterozygous Irs1(+)(/sml) mice raise the possibility that similar mutations in humans are associated with short stature or osteoporosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.