Long term breeding of the Lmna G609G progeric mouse: Characterization of homozygous and heterozygous models

Zaghini, Anna; Sarli, Giuseppe; Barboni, Catia; Sanapo, Mara; Pellegrino, Valeria; Diana, Alessia; Linta, Nikolina; Rambaldi, Julie; D’Apice, Maria Rosaria; Murdocca, Michela; Baleani, Massimiliano; Baruffaldi, Fabio; Fognani, Roberta; Mecca, R.; Festa, Anna; Papparella, Serenella; Paciello, Orlando; Prisco, Francesco; Capanni, Cristina; Loi, Manuela; Schena, Elisa; Lattanzi, Giovanna; Squarzoni, Stefano

doi:10.1016/j.exger.2019.110784

Cited by 19 publications

(30 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KI 28,30 and abnormalities of the incisors were evaluated. Data processing and analysis were performed using a RadiAnt DICOM system in Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University (Jinju, Korea).…”

Section: Methodsmentioning

confidence: 99%

“…S11c) of untreated Lmna G609G/+ mice compared with Lmna +/+ mice and progerin-treated Lmna G609G/+ mice. Lmna G609G transgenic mice are known to show defects in skin tissues 28 . In the present study, epidermis of foot pad skin was thickened and dermal connective tissue was enriched in progerinin-treated Lmna G609G/+ mice (Fig.…”

Section: Slc-d011 Ameliorates the Premature Aging Characteristics Of mentioning

confidence: 99%

“…4f) known to be reduced in a mouse model of HGPS 29 . Acquisition of kyphosis and dental abnormality are characteristics of Lmna G609G transgenic mice 22,28,30 . The mean kyphosis index (KI) of wild-type mice was >4.…”

Section: Slc-d011 Ameliorates the Premature Aging Characteristics Of mentioning

confidence: 99%

“…4g). Their lower incisors grew toward the palate because of malocclusion 28 . Progerinin ameliorated these abnormalities of Lmna G609G/+ mice (Fig.…”

Section: Slc-d011 Ameliorates the Premature Aging Characteristics Of mentioning

confidence: 99%

See 3 more Smart Citations

Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome

et al. 2021

View full text Add to dashboard Cite

Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient’s cells, and very short life span in an in vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated in in vivo pharmacokinetic (PK) analysis. Thus, we improved its property through chemical modification and obtained an optimized drug candidate, Progerinin (SLC-D011). This chemical can extend the life span of LmnaG609G/G609G mouse for about 10 weeks and increase its body weight. Progerinin can also extend the life span of LmnaG609G/+ mouse for about 14 weeks via oral administration, whereas treatment with lonafarnib (farnesyl-transferase inhibitor) can only extend the life span of LmnaG609G/+ mouse for about two weeks. In addition, progerinin can induce histological and physiological improvement in LmnaG609G/+ mouse. These results indicate that progerinin is a strong drug candidate for HGPS.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Slc-d011 Ameliorates the Premature Aging Characteristics Of mentioning

confidence: 99%

Section: Slc-d011 Ameliorates the Premature Aging Characteristics Of mentioning

confidence: 99%

“…4g). Their lower incisors grew toward the palate because of malocclusion 28 . Progerinin ameliorated these abnormalities of Lmna G609G/+ mice (Fig.…”

Section: Slc-d011 Ameliorates the Premature Aging Characteristics Of mentioning

confidence: 99%

See 2 more Smart Citations

Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome

et al. 2021

View full text Add to dashboard Cite

show abstract

“…To generate a new mouse model to study atherosclerosis in HGPS, we crossed atheroprone Ldlr −/− mice with progeroid Lmna G609G mice, which carry a c.1827C>T; p.G609G mutation in the Lmna gene and, like HGPS patients, produce progerin through aberrant splicing [ 14 , 16 ]. Homozygous Ldlr −/− Lmna G609G/G609G and heterozygous Ldlr −/− Lmna G609G /+ mice both had a shorter lifespan and lower body weight than control Ldlr −/− Lmna +/+ mice with normal lamin A expression ( Figure 1 a,b for males; Figure A1 a,b for females) and showed an aging phenotype with progressive fat loss closely resembling that of progeric mice without Ldlr deficiency.…”

Section: Resultsmentioning

confidence: 99%

Premature Vascular Aging with Features of Plaque Vulnerability in an Atheroprone Mouse Model of Hutchinson–Gilford Progeria Syndrome with Ldlr Deficiency

Nevado

Hamczyk

Gonzalo

et al. 2020

Cells

View full text Add to dashboard Cite

Hutchinson–Gilford progeria syndrome (HGPS) is among the most devastating of the laminopathies, rare genetic diseases caused by mutations in genes encoding nuclear lamina proteins. HGPS patients age prematurely and die in adolescence, typically of atherosclerosis-associated complications. The mechanisms of HGPS-related atherosclerosis are not fully understood due to the scarcity of patient-derived samples and the availability of only one atheroprone mouse model of the disease. Here, we generated a new atherosusceptible model of HGPS by crossing progeroid LmnaG609G/G609G mice, which carry a disease-causing mutation in the Lmna gene, with Ldlr−/− mice, a commonly used preclinical atherosclerosis model. Ldlr−/−LmnaG609G/G609G mice aged prematurely and had reduced body weight and survival. Compared with control mice, Ldlr−/−LmnaG609G/G609G mouse aortas showed a higher atherosclerosis burden and structural abnormalities typical of HGPS patients, including vascular smooth muscle cell depletion in the media, adventitial thickening, and elastin structure alterations. Atheromas of Ldlr−/−LmnaG609G/G609G mice had features of unstable plaques, including the presence of erythrocytes and iron deposits and reduced smooth muscle cell and collagen content. Ldlr−/−LmnaG609G/G609G mice faithfully recapitulate vascular features found in patients and thus provide a new tool for studying the mechanisms of HGPS-related atherosclerosis and for testing therapies.

show abstract

Spinal malformation − A biochemical analysis using congenital kyphosis rats

Shimokawa

Takahashi

Iizuka

2022

J of Cellular Biochemistry

View full text Add to dashboard Cite

Spinal kyphosis involves the vertebrae curving excessively backward, beyond their physiological curvature. Although the normal structure of the spinal vertebrae is extremely important for maintaining posture, the normal function of the thoracic and abdominal organs, and cosmetics, our knowledge concerning the pathogenesis of this disease is lacking. Furthermore, the responsible gene has not yet been identified. In this short review, we summarize the current state of kyphosis research and introduce the molecular and cellular mechanisms associated with the pathogenesis of this disease, based on findings obtained using rats that develop kyphosis.

show abstract

Long term breeding of the Lmna G609G progeric mouse: Characterization of homozygous and heterozygous models

Cited by 19 publications

References 46 publications

Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome

Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome

Premature Vascular Aging with Features of Plaque Vulnerability in an Atheroprone Mouse Model of Hutchinson–Gilford Progeria Syndrome with Ldlr Deficiency

Spinal malformation − A biochemical analysis using congenital kyphosis rats

Contact Info

Product

Resources

About