The lateral meningocele syndrome mutation causes marked osteopenia in mice

Canalis, Ernesto; Yu, Jungeun; Schilling, Lauren; Yee, Siu‐Pok; Zanotti, Stefano

doi:10.1074/jbc.ra118.004242

Cited by 33 publications

(58 citation statements)

References 81 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Total RNA was extracted from cells with the RNeasy kit (Qiagen, Valencia, CA) in accordance with manufacturer's instructions (Canalis et al, 2016; Canalis et al, 2018; Nazarenko, Lowe et al, 2002; Nazarenko, Pires, Lowe, Obaidy, & Rashtchian, 2002). Equal amounts of RNA were reverse‐transcribed using the iScript RT‐PCR kit (BioRad, Carlsbad, CA) and amplified in the presence of specific primers (all primers from Integrated DNA Technologies, Coralville, IA; Table 1) with the iQ SYBR Green Supermix or SsoAdvanced TM Universal SYBR Green Supermix (BioRad) at 60°C for 40 cycles.…”

Section: Methodsmentioning

confidence: 99%

Nuclear factor of activated T cells 1 and 2 are required for vertebral homeostasis

Canalis

Schilling

Eller

et al. 2020

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

The present study defines the function of nuclear factor of activated T cells (NFAT)c1 and NFATc2 in osteoblast function in vivo and in vitro. Nfatc1loxP/loxP, Nfatc2loxP/loxP, and Nfatc1loxP/loxP;Nfatc2loxP/loxP conditional mice were mated with BGLAP‐Cre transgenics to inactivate Nfatc1 and Nfatc2 singly and in combination in osteoblasts. Microcomputed tomography demonstrated that male and female conditionally inactivated Nfatc1, Nfatc2 and dual Nfatc1;Nfatc2 mice had osteopenia at Lumbar 3 (L3) sites when compared to littermate controls. However, the Nfatc1 and Nfatc2 inactivation singly and in combination in Bglap‐expressing osteoblasts did not result in an appreciable phenotype at femoral sites. Bone histomorphometry of L3 confirmed the osteopenic phenotype and demonstrated that Nfatc1;Nfatc2 inactivated male mice had a significant decrease in osteoblast number and in osteoblast surface and osteoid surface. The dual downregulation of Nfatc1 and Nfatc2 in bone marrow stromal cells caused a decrease in Alpl and Bglap expression, confirming a role of these transcription factors in osteoblast function. In conclusion, our studies reveal that NFATc1 and NFATc2 are necessary for optimal vertebral, but not femoral, bone homeostasis in vivo and osteoblast differentiation in vitro.

show abstract

Section: Methodsmentioning

confidence: 99%

Nuclear factor of activated T cells 1 and 2 are required for vertebral homeostasis

Canalis

Schilling

Eller

et al. 2020

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…One group created a human lateral meningocele syndrome (LMS)-related mutant mouse model of the Notch3 gene via microinjection of the Cas9 mRNA and gRNA. The LMS-related mutant mouse model induced a 35%-60% decrease in the cancellous bone volume, together with a reduction in trabecular number, which mimics the skeletal manifestation of lateral meningocele syndrome (Canalis et al 2018). In addition, several studies have reported mouse models of osteoporosis that were generated by knocking out the ATP6V1H gene, a subunit of V- Figure 1.…”

Section: Mice and Ratsmentioning

confidence: 99%

Genome editing methods in animal models

Lee

Yoon

Kim

2020

Animal Cells and Systems

View full text Add to dashboard Cite

Genetically engineered animal models that reproduce human diseases are very important for the pathological study of various conditions. The development of the clustered regularly interspaced short palindromic repeats (CRISPR) system has enabled a faster and cheaper production of animal models compared with traditional gene-targeting methods using embryonic stem cells. Genome editing tools based on the CRISPR-Cas9 system are a breakthrough technology that allows the precise introduction of mutations at the target DNA sequences. In particular, this accelerated the creation of animal models, and greatly contributed to the research that utilized them. In this review, we introduce various strategies based on the CRISPR-Cas9 system for building animal models of human diseases and describe various in vivo delivery methods of CRISPR-Cas9 that are applied to disease models for therapeutic purposes. In addition, we summarize the currently available animal models of human diseases that were generated using the CRISPR-Cas9 system and discuss future directions. ARTICLE HISTORY

show abstract

“…Expectedly, CRISPR/Cas9 gene editing in these mouse and zebrafish models of human skeletal disease has swiftly evolved as comprehensively reviewed, by Wu et al ( 189 ). To date, CRISPR/Cas9 models have been done for several skeletal disorders such as OI ( 190 ), meningocele syndrome ( 191 ) and campomelic dysplasia ( 192 ). OI type V is a rare autosomal dominant disease characterized by increased bone fragility, low BMD and increased susceptibility to bone fracture followed by hyperplastic callus formation.…”

Section: Current Progress In Gene Editing For Monogenic and Complex Bmentioning

confidence: 99%

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

Trajanoska

Rivadeneira

2020

Front. Endocrinol.

View full text Add to dashboard Cite

Current genetic studies of monogenic and complex bone diseases have broadened our understanding of disease pathophysiology, highlighting the need for medical interventions and treatments tailored to the characteristics of patients. As genomic research progresses, novel insights into the molecular mechanisms are starting to provide support to clinical decision-making; now offering ample opportunities for disease screening, diagnosis, prognosis and treatment. Drug targets holding mechanisms with genetic support are more likely to be successful. Therefore, implementing genetic information to the drug development process and a molecular redefinition of skeletal disease can help overcoming current shortcomings in pharmaceutical research, including failed attempts and appalling costs. This review summarizes the achievements of genetic studies in the bone field and their application to clinical care, illustrating the imminent advent of the genomic medicine era.

show abstract

The lateral meningocele syndrome mutation causes marked osteopenia in mice

Cited by 33 publications

References 81 publications

Nuclear factor of activated T cells 1 and 2 are required for vertebral homeostasis

Nuclear factor of activated T cells 1 and 2 are required for vertebral homeostasis

Genome editing methods in animal models

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

Contact Info

Product

Resources

About