- Lee S.Y.
- Kumano K.
- Nakazaki K.
- Sanada M.
- Matsumoto A.
- Yamamoto G.
- Nannya Y.
- Suzuki R.
- Ota S.
- Ota Y.
- Izutsu K.
- Sakata-Yanagimoto M.
- Hangaishi A.
- Yagita H.
- Fukayama M.
- Seto M.
- Kurokawa M.
- Ogawa S.
- Chiba S.
- Descatoire M.
- Weller S.
- Irtan S.
- Sarnacki S.
- Feuillard J.
- Storck S.
- Guiochon-Mantel A.
- Bouligand J.
- Morali A.
- Cohen J.
- Jacquemin E.
- Iascone M.
- Bole-Feysot C.
- Cagnard N.
- Weill J.C.
- Reynaud C.A.
- Isidor B.
- Lindenbaum P.
- Pichon O.
- Bezieau S.
- Dina C.
- Jacquemont S.
- Martin-Coignard D.
- Thauvin-Robinet C.
- Le M.M.
- Mandel J.L.
- David A.
- Faivre L.
- Cormier-Daire V.
- Redon R.
- Le C.C.
- Simpson M.A.
- Irving M.D.
- Asilmaz E.
- Gray M.J.
- Dafou D.
- Elmslie F.V.
- Mansour S.
- Holder S.E.
- Brain C.E.
- Burton B.K.
- Kim K.H.
- Pauli R.M.
- Aftimos S.
- Stewart H.
- Kim C.A.
- Holder-Espinasse M.
- Robertson S.P.
- Drake W.M.
- Trembath R.C.
- Isidor B.
- Lindenbaum P.
- Pichon O.
- Bezieau S.
- Dina C.
- Jacquemont S.
- Martin-Coignard D.
- Thauvin-Robinet C.
- Le M.M.
- Mandel J.L.
- David A.
- Faivre L.
- Cormier-Daire V.
- Redon R.
- Le C.C.
- Simpson M.A.
- Irving M.D.
- Asilmaz E.
- Gray M.J.
- Dafou D.
- Elmslie F.V.
- Mansour S.
- Holder S.E.
- Brain C.E.
- Burton B.K.
- Kim K.H.
- Pauli R.M.
- Aftimos S.
- Stewart H.
- Kim C.A.
- Holder-Espinasse M.
- Robertson S.P.
- Drake W.M.
- Trembath R.C.
- Fukushima H.
- Shimizu K.
- Watahiki A.
- Hoshikawa S.
- Kosho T.
- Oba D.
- Sakano S.
- Arakaki M.
- Yamada A.
- Nagashima K.
- Okabe K.
- Fukumoto S.
- Jimi E.
- Bigas A.
- Nakayama K.I.
- Nakayama K.
- Aoki Y.
- Wei W.
- Inuzuka H.
Materials and Methods
Mouse Models
Notch2 COIN Mice
- Economides A.N.
- Frendewey D.
- Yang P.
- Dominguez M.G.
- Dore A.T.
- Lobov I.B.
- Persaud T.
- Rojas J.
- McClain J.
- Lengyel P.
- Droguett G.
- Chernomorsky R.
- Stevens S.
- Auerbach W.
- DeChiara T.M.
- Pouyemirou W.
- Cruz Jr., J.M.
- Feeley K.
- Mellis I.A.
- Yasenchack J.
- Hatsell S.J.
- Xie L.
- Latres E.
- Huang L.
- Zhang Y.
- Pefanis E.
- Skokos D.
- Deckelbaum R.A.
- Croll S.D.
- Davis S.
- Valenzuela D.M.
- Gale N.W.
- Murphy A.J.
- Yancopoulos G.D.
Induction of the HCS Mutation in the Germline and in CD19-Expressing Cells
Induction of the NOTCH1-NICD in CD19-Expressing Cells
Hajdu-Cheney Global Notch2tm1.1ECan Mutant Mice
Genotyping and Verification of LoxP Recombination
Allele | Strand | Sequence | Amplicon size, bp |
---|---|---|---|
Genotyping | |||
CD19Cre | Forward | 5′-GCGGTCTGGCAGTAAAAACTATC-3′ | 100 |
Reverse | 5′-GTGAAACAGCATTGCTGTCACTT-3′ | ||
CD19WT | Forward | 5′-CCTCTCCCTGTCTCCTTCCT-3′ | 500 |
Reverse | 5′-TGGTCTGAGACATTGACAATCA-3′ | ||
Fabp1 | Forward | 5′-TGGACAGGACTGGACCTCTGCTTTCC-3′ | 200 |
Reverse | 5′-TAGAGCTTTGCCACATCACAGGTCAT-3′ | ||
HprtWT | Forward | 5′-TTTCTATAGGACTGAAAGACTTGCTC-3′ | 200 |
Reverse | 5′-CACAGTAGCTCTTCAGTCTGATAAAA-3′ | ||
HprtCre | Forward | 5′-GCGGTCTGGCAGTAAAAACTATC-3′ | 100 |
Reverse | 5′-GTGAAACAGCATTGCTGTCACTT-3′ | ||
Notch2[ΔPEST]COIN | Forward | 5′-CCGGGCCGCGACTGAAACCCTAG-3′ | 330 |
Reverse | 5′-CCACCACCTCCAGGAGTTGGGC-3′ | ||
Notch2tm1.1ECan | Forward Nch2Lox gtF | 5′-CCCTTCTCTCTGTGCGGTAG-3′ | WT = 310 Notch2tm1.1ECan = 400 |
Reverse Nch2Lox gtR | 5′-CTCAGAGCCAAAGCCTCACTG-3′ | ||
Notch2WT | Forward | 5′-GCTCAGACCATTGTGCCAACCTAT-3′ | 100 |
Reverse | 5′-CAGCAGCATTTGAGGAGGCGTAA-3′ | ||
RosaNotch1 | Forward | 5′-GGAGCGGGAGAAATGGATATG-3′ | WT = 600 RosaNotch1 NICD = 250 |
Reverse WT | 5′-AAAGTCGCTCTGAGTTGTTATTG-3′ | ||
Reverse RosaNotch1 NICD | 5′-GCGAAGAGTTTGTCCTCAACC-3′ | ||
LoxP recombination | |||
Notch2[ΔPEST]COIN | Forward | 5′-GTACTTCAGCACAGTTTTAGAGAAC-3′ | Not recombined and not detected Recombined = 250 |
Reverse | 5′-GTGAGTCACCCGCCGGATGTC-3′ | ||
RosaNotch1 | Forward | 5′-TTCGCGGTCTTTCCAGTGG-3′ | Not recombined = 500 Recombined = 300 |
Reverse absent loxP recombination | 5′-AGCCTCTGAGCCCAGAAAGC-3′ | ||
Reverse present loxP recombination | 5′-GCCGACTGAGTCCTCGCC-3′ |
Splenectomies
Immunofluorescence
Flow Cytometry
RNA Extraction from Spleen and Bone Marrow Cells and RNA Integrity
Quantitative RT-PCR
Gene | Sequence | GenBank accession no. |
---|---|---|
Cre | F: 5′-TGTTAATCCATATTGGCAGAACGA-3′ | X03453 |
R: 5′-ATCCATCGCTCGACCAGTTTA-3′ | ||
Dll1 | F: 5′-CTCTTCCCCTTGTTCTAAC-3′ | NM_007865 |
R: 5′-ACAGTCATCCACATTGTC-3′ | ||
Dll3 | F: 5′-TCTATCTTGTCCCTTCTCTATCA-3′ | NM_007866 |
R: 5′-AATCATTCAGGCTCCATCTC-3′ | ||
Dll4 | F: 5′-TGACAAGAGCTTAGGAGAG-3′ | NM_019454 |
R: 5′-GCTTCTCACTGTGTAACC-3′ | ||
Hes1 | F: 5′-ACCAAAGACGGCCTCTGAGCACAGAAAGT-3′ | NM_008235 |
R: 5′-ATTCTTGCCCTTCGCCTCTT-3′ | ||
Hes5 | F: 5′-GGAGATGCTCAGTCCCAAGGAG-3′ | NM_010419 |
R: 5′-TGCTCTATGCTGCTGTTGATGC-3′ | ||
Jag1 | F: 5′-TGGGAACTGTTGTGGTGGAGTCCG-3′ | NM_013822 |
R: 5′-GTGACGCGGGACTGATACTCCT-3′ | ||
Jag2 | F: 5′-AAGGTGGAAACAGTTGT-3′ | NM_010588 |
R: 5′-CACGGGCACCAACAG-3′ | ||
Notch1 | F: 5′-GTCCCACCCATGACCACTACCCAGTTC-3′ | NM_008714 |
R: 5′-GGGTGTTGTCCACAGGTGA-3′ | ||
Notch1NICD | F: 5′-GTGCTCTGATGGACGACAAT-3′ | NM_008714 |
R: 5′-GCTCCTCAAACCGGAACTTC-3′ | ||
Notch2PEST | F: 5′-CCATTGTGCCAACCTATCAT-3′ | NM_010928 |
R: 5′-TTGAGGAGGCGTAACTGT-3′ | ||
Notch2ΔPEST | F: 5′-GGCTTTCCCACCTACCAT-3′ | Not applicable |
R: 5′-TAGTCGGGCACGTCGTAG-3′ | ||
Notch2 | F: 5′-TGACGTTGATGAGTGTATCTCCAAGCC-3′ | NM_010928 |
R: 5′-GTAGCTGCCCTGAGTGTTGTGG-3′ | ||
Notch3 | F: 5′-CCGATTCTCCTGTCGTTGTCTCC-3′ | NM_008716 |
R: 5′-TGAACACAGGGCCTGCTGAC-3′ | ||
Notch4 | F: 5′-CCAGCAGACAGACTACGGTGGAC-3′ | NM_010929 |
R: 5′-GCAGCCAGCATCAAAGGTGT-3′ | ||
Rpl38 | F: 5′-AGAACAAGGATAATGTGAAGTTCAAGGTTC-3′ | NM_001048057; NM_001048058; NM_023372 |
R: 5′-CTGCTTCAGCTTCTCTGCCTTT-3′ | ||
Tnfrsf11b | F: 5′-CAGAAAGGAAATGCAACACATGACAAC-3′ | NM_009399 |
R: 5′-GCCTCTTCACACAGGGTGACATC-3′ | ||
Tnfsf11 | F: 5′-TATAGAATCCTGAGACTCCATGAAAAC-3′ | NM_011613 |
R: 5′-CCCTGAAAGGCTTGTTTCATCC-3′ |
Microcomputed Tomography
Statistical Analysis
Results
Expression Pattern of Notch Receptors and Ligands in the Spleen and Bone Marrow

Inversion of the Notch2[ΔPEST]COIN Allele in the Germline Increases Marginal Zone B Cells


Inversion of the Notch2[ΔPEST]COIN Allele in CD19 B Cells Causes an Expansion of Marginal Zone B Cells

Gate used | B220+ IgM− | B220+CD19+CD117− | ||
---|---|---|---|---|
CD19− CD117− pre–pro-B | CD19+ CD117+ pro-B | CD19+ CD117− pre-B | IgM+ immature B | |
Notch2ΔPEST/ΔPEST | ||||
Male | ||||
Control | 30.5 ± 5.1 | 0.5 ± 0.1 | 66.0 ± 6.1 | 74.6 ± 3.2 |
Notch2ΔPEST | 27.2 ± 3.0 | 0.4 ± 0.1 | 69.7 ± 2.9 | 68.8 ± 4.1 |
Female | ||||
Control | 29.2 ± 3.7 | 0.5 ± 0.2 | 67.3 ± 3.5 | 71.5 ± 1.6 |
Notch2ΔPEST | 24.7 ± 4.4 | 0.4 ± 0.0 | 72.9 ± 4.6 | 69.6 ± 5.5 |
RosaNotch1 | ||||
Male | ||||
Control | 20.5 ± 0.9 | 1.1 ± 0.1 | 76.7 ± 1.0 | 66.1 ± 1.8 |
RosaNotch1 | 26.0 ± 1.7 | 0.9 ± 0.1 | 72.9 ± 3.4 | 67.3 ± 1.0 |
Female | ||||
Control | 26.1 ± 2.3 | 0.8 ± 0.1 | 69.7 ± 4.5 | 67.3 ± 1.2 |
RosaNotch1 | 31.4 ± 6.0 | 0.8 ± 0.3 | 67.5 ± 7.8 | 73.2 ± 4.0 |

Induction of the NOTCH1-NICD in CD19 B-Cell Phenocopies CD19Cre/WT;Notch2ΔPEST/ΔPEST Mice


Prolonged Activation of Notch in the B-Cell Lineage Does Not Cause a Skeletal Phenotype
Variable | Males | Females | ||
---|---|---|---|---|
Control (n = 5) | Notch2ΔPEST (n = 7) | Control (n = 7) | Notch2ΔPEST (n = 6) | |
Distal femur trabecular bone | ||||
Bone/total volume, % | 12.6 ± 1.2 | 14.9 ± 2.3 | 5.3 ± 0.9 | 6.2 ± 2.4 |
Trabecular separation, μm | 153 ± 11 | 143 ± 17 | 226 ± 9 | 214 ± 27 |
Trabecular no., 1/mm | 6.5 ± 0.5 | 7.0 ± 0.7 | 4.5 ± 0.2 | 4.8 ± 0.6 |
Trabecular thickness, μm | 33 ± 1 | 35 ± 1 | 28 ± 1 | 28 ± 3 |
Connectivity density, 1/mm3 | 487 ± 96 | 641 ± 151 | 134 ± 46 | 187 ± 103 |
Structure-model index | 2.2 ± 0.1 | 2.2 ± 0.2 | 2.7 ± 0.2 | 2.6 ± 0.3 |
Density of material, mg HA/cm3 | 1053 ± 10 | 1047 ± 21 | 1039 ± 16 | 1027 ± 18 |
Femoral midshaft cortical bone | ||||
Bone/total volume, % | 91.4 ± 0.8 | 91.4 ± 1.4 | 86.1 ± 1.3 | 86.6 ± 2.2 |
Porosity, % | 8.6 ± 0.8 | 8.3 ± 1.4 | 13.9 ± 1.3 | 13.4 ± 2.2 |
Cortical thickness, μm | 178 ± 6 | 177 ± 13 | 130 ± 7 | 130 ± 17 |
Total area, mm2 | 2.2 ± 0.1 | 2.2 ± 0.1 | 1.7 ± 0.1 | 1.7 ± 0.2 |
Bone area, mm2 | 0.9 ± 0.2 | 1.0 ± 0.1 | 0.7 ± 0.1 | 0.7 ± 0.1 |
Periosteal perimeter, μm | 5.3 ± 0.1 | 5.2 ± 0.2 | 4.6 ± 0.1 | 4.7 ± 0.2 |
Endocortical perimeter, mm | 3.9 ± 0.2 | 3.8 ± 0.2 | 3.6 ± 0.1 | 3.6 ± 0.2 |
Density of material, mg HA/cm3 | 1138 ± 37 | 1131 ± 33 | 1136 ± 22 | 1122 ± 2.5 |
Variables | Males | Females | ||
---|---|---|---|---|
Control (n = 7) | RosaNotch1 (n = 5) | Control (n = 6) | RosaNotch1 (n = 3) | |
Distal femur trabecular bone | ||||
Bone/total volume, % | 9.3 ± 4.4 | 7.4 ± 3.0 | 5.1 ± 1.5 | 5.0 ± 0.6 |
Trabecular separation, μm | 188 ± 28 | 199 ± 21 | 228 ± 17 | 227 ± 12 |
Trabecular no., 1/mm | 5.4 ± 0.8 | 5.1 ± 0.6 | 4.4 ± 0.3 | 4.4 ± 0.2 |
Trabecular thickness, μm | 33 ± 5 | 32 ± 4 | 30 ± 2 | 28 ± 1 |
Connectivity density, 1/mm3 | 274 ± 180 | 197 ± 138 | 109 ± 45 | 109 ± 33 |
Structure-model index | 2.4 ± 0.4 | 2.7 ± 0.3 | 2.8 ± 0.2 | 2.7 ± 0.1 |
Density of material, mg HA/cm3 | 1023 ± 16 | 1017 ± 16 | 1009 ± 17 | 1014 ± 13 |
Femoral midshaft cortical bone | ||||
Bone/total volume, % | 86.6 ± 2.7 | 85.7 ± 2.6 | 86.6 ± 2.9 | 85.6 ± 1.2 |
Porosity, % | 13.4 ± 2.7 | 14.3 ± 2.6 | 13.4 ± 2.9 | 14.4 ± 1.2 |
Cortical thickness, μm | 148 ± 20 | 138 ± 19 | 133 ± 17 | 130 ± 7 |
Total area, mm2 | 1.9 ± 0.2 | 1.7 ± 0.2 | 1.6 ± 0.1 | 1.6 ± 0.1 |
Bone area, mm2 | 0.8 ± 0.1 | 0.8 ± 0.1 | 0.7 ± 0.1 | 0.7 ± 0.1 |
Periosteal perimeter, μm | 4.8 ± 0.3 | 4.7 ± 0.2 | 4.5 ± 0.2 | 4.5 ± 0.1 |
Endocortical perimeter, mm | 3.6 ± 0.2 | 3.5 ± 0.1 | 3.4 ± 0.1 | 3.4 ± 0.1 |
Density of material, mg HA/cm3 | 1137 ± 14 | 1132 ± 11 | 1158 ± 22 | 1141 ± 1.2 |
Changes in B-Cell Allocation in the Spleen Do Not Affect the Skeleton
Males | Sham | Splenectomy | ||
---|---|---|---|---|
Control (n = 6) | Notch2tm1.1ECan (n = 5) | Control (n = 7) | Notch2tm1.1ECan (n = 4) | |
Distal femur trabecular bone | ||||
Bone/total volume, % | 8.8 ± 2.7 | 5.2 ± 3.2 | 11.1 ± 3.5 | 4.0 ± 2.9 |
Trabecular separation, μm | 207 ± 11 | 281 ± 39 | 201 ± 36 | 333 ± 79 |
Trabecular no., 1/mm | 4.9 ± 0.3 | 3.7 ± 0.6 | 5.1 ± 0.8 | 3.2 ± 0.8 |
Trabecular thickness, μm | 39 ± 6 | 35 ± 7 | 44 ± 5 | 32 ± 6 |
Connectivity density, 1/mm3 | 215 ± 71 | 123 ± 105 | 269 ± 83 | 85 ± 76 |
Structure-model index | 2.8 ± 0.3 | 3.1 ± 0.4 | 2.7 ± 0.3 | 3.1 ± 0.5 |
Density of material, mg HA/cm3 | 855 ± 18 | 819 ± 26 | 867 ± 25 | 800 ± 29 |
Femoral midshaft cortical bone | ||||
Bone/total volume, % | 87.5 ± 1.3 | 83.9 ± 4.6 | 87.8 ± 1.6 | 83.8 ± 2.6 |
Porosity, % | 12.5 ± 1.3 | 16.1 ± 4.6 | 12.2 ± 1.6 | 16.2 ± 2.6 |
Cortical thickness, μm | 148 ± 13 | 119 ± 21 | 152 ± 11 | 116 ± 13 |
Total area, mm2 | 1.8 ± 0.3 | 1.6 ± 0.3 | 1.9 ± 0.2 | 1.7 ± 0.2 |
Bone area, mm2 | 0.8 ± 0.1 | 0.6 ± 0.1 | 0.8 ± 0.1 | 0.6 ± 0.1 |
Periosteal perimeter, mm | 4.8 ± 0.3 | 4.4 ± 0.5 | 4.9 ± 0.3 | 4.7 ± 0.3 |
Endocortical perimeter, mm | 3.6 ± 0.2 | 3.4 ± 0.3 | 3.7 ± 0.3 | 3.7 ± 0.3 |
Density of material, mg HA/cm3 | 1119 ± 16 | 1093 ± 35 | 1123 ± 21 | 1083 ± 22 |
Females | Sham | Splenectomy | ||
Control (n = 5) | Notch2tm1.1ECan (n = 5) | Control (n = 4) | Notch2tm1.1ECan (n = 6) | |
Distal femur trabecular bone | ||||
Bone/total volume, % | 5.5 ± 1.0 | 2.6 ± 1.1 | 4.8 ± 1.4 | 2.9 ± 1.6 |
Trabecular separation, μm | 261 ± 20 | 355 ± 72 | 272 ± 57 | 402 ± 109 |
Trabecular no., 1/mm | 3.9 ± 0.3 | 2.9 ± 0.6 | 3.8 ± 0.7 | 2.7 ± 0.7 |
Trabecular thickness, μm | 35 ± 2 | 29 ± 3 | 33 ± 1 | 30 ± 3 |
Connectivity density, 1/mm3 | 158 ± 56 | 57 ± 37 | 118 ± 54 | 69 ± 44 |
Structure-model index | 2.8 ± 0.2 | 3.1 ± 0.2 | 3.0 ± 0.1 | 3.0 ± 0.2 |
Density of material, mg HA/cm3 | 843 ± 16 | 825 ± 7 | 844 ± 16 | 813 ± 24 |
Femoral midshaft cortical bone | ||||
Bone/total volume, % | 87.1 ± 0.8 | 84.1 ± 3.0 | 85.7 ± 2.2 | 79.9 ± 7.0 |
Porosity, % | 12.9 ± 0.8 | 15.9 ± 3.0 | 14.3 ± 2.2 | 20.1 ± 7.0 |
Cortical thickness, μm | 136 ± 10 | 119 ± 18 | 128 ± 14 | 101 ± 23 |
Total area, mm2 | 1.6 ± 0.1 | 1.4 ± 0.1 | 1.5 ± 0.1 | 1.5 ± 0.1 |
Bone area, mm2 | 0.7 ± 0.1 | 0.6 ± 0.1 | 0.6 ± 0.1 | 0.5 ± 0.1 |
Periosteal perimeter, mm | 4.4 ± 0.1 | 4.1 ± 0.2 | 4.4 ± 0.1 | 4.3 ± 0.2 |
Endocortical perimeter, mm | 3.4 ± 0.1 | 3.1 ± 0.3 | 3.4 ± 0.1 | 3.4 ± 0.3 |
Density of material, mg HA/cm3 | 1123 ± 9 | 1099 ± 47 | 1111 ± 20 | 1057 ± 43 |
Discussion
- Descatoire M.
- Weller S.
- Irtan S.
- Sarnacki S.
- Feuillard J.
- Storck S.
- Guiochon-Mantel A.
- Bouligand J.
- Morali A.
- Cohen J.
- Jacquemin E.
- Iascone M.
- Bole-Feysot C.
- Cagnard N.
- Weill J.C.
- Reynaud C.A.
Acknowledgments
Supplemental Data
- Data Profile
References
- Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain.Nature. 1998; 393: 382-386
- Notch and the skeleton.Mol Cell Biol. 2010; 30: 886-896
- More complicated than it looks: assembly of Notch pathway transcription complexes.Oncogene. 2008; 27: 5099-5109
- Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes.Cell. 2006; 124: 973-983
- Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA.Cell. 2006; 124: 985-996
- HES and HERP families: multiple effectors of the Notch signaling pathway.J Cell Physiol. 2003; 194: 237-255
- Characterization of CSL (CBF-1, Su(H), Lag-1) mutants reveals differences in signaling mediated by Notch1 and Notch2.J Biol Chem. 2012; 287: 34904-34916
- Deficient T cell fate specification in mice with an induced inactivation of Notch1.Immunity. 1999; 10: 547-558
- T cell acute lymphoblastic leukemia/lymphoma: a human cancer commonly associated with aberrant NOTCH1 signaling.Curr Opin Hematol. 2004; 11: 426-433
- Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma.Cancer Sci. 2009; 100: 920-926
- The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development.J Exp Med. 2012; 209: 1537-1551
- Activated Notch2 potentiates CD8 lineage maturation and promotes the selective development of B1 B cells.Mol Cell Biol. 2003; 23: 8637-8650
- Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells.Nat Immunol. 2002; 3: 443-450
- Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development.Immunity. 2003; 18: 675-685
- Notch2 haploinsufficiency results in diminished B1 B cells and a severe reduction in marginal zone B cells.J Immunol. 2003; 171: 2783-2788
- Identification of a human splenic marginal zone B cell precursor with NOTCH2-dependent differentiation properties.J Exp Med. 2014; 211: 987-1000
- CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling.Blood. 2011; 118: 6321-6331
- Hajdu Cheney syndrome: report of a novel NOTCH2 mutation and treatment with denosumab.Bone. 2016; 92: 150-156
- Hajdu-Cheney syndrome: a review.Orphanet J Rare Dis. 2014; 9: 200
- Hajdu-Cheney syndrome, a disease associated with NOTCH2 mutations.Curr Osteoporos Rep. 2016; 14: 126-131
- Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu-Cheney syndrome.Eur J Hum Genet. 2012; 20: 122-124
- Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis.Nat Genet. 2011; 43: 306-308
- Mutations in NOTCH2 in families with Hajdu-Cheney syndrome.Hum Mutat. 2011; 32: 1114-1117
- Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss.Nat Genet. 2011; 43: 303-305
- Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome.Osteoporos Int. 2013; 24: 2275-2281
- Hajdu Cheney mouse mutants exhibit osteopenia, increased osteoclastogenesis and bone resorption.J Biol Chem. 2016; 291: 1538-1551
- NOTCH2 Hajdu-Cheney mutations escape SCF(FBW7)-dependent proteolysis to promote osteoporosis.Mol Cell. 2017; 68: 645-658.e5
- The Hajdu Cheney mutation is a determinant of B-cell allocation of the splenic marginal zone.Am J Pathol. 2018; 188: 149-159
- How B cells influence bone biology in health and disease.Bone. 2010; 47: 472-479
- B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo.Blood. 2007; 109: 3839-3848
- Tight relationships between B lymphocytes and the skeletal system.Trends Mol Med. 2014; 20: 405-412
- B cell production of both OPG and RANKL is significantly increased in aged mice.Open Bone J. 2014; 6: 8-17
- Production of RANKL by memory B cells: a link between B cells and bone erosion in rheumatoid arthritis.Arthritis Rheumatol. 2016; 68: 805-816
- Receptor activator of nuclear factor kappaB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss.J Biol Chem. 2012; 287: 29851-29860
- Sustained Notch2 signaling in osteoblasts, but not in osteoclasts, is linked to osteopenia in a mouse model of Hajdu-Cheney syndrome.J Biol Chem. 2017; 292: 12232-12244
- Notch signaling controls multiple steps of pancreatic differentiation.Proc Natl Acad Sci U S A. 2003; 100: 14920-14925
- Conditionals by inversion provide a universal method for the generation of conditional alleles.Proc Natl Acad Sci U S A. 2013; 110: E3179-E3188
- A Cre/loxP-deleter transgenic line in mouse strain 129S1/SvImJ.Genesis. 2002; 32: 199-202
- B lymphocyte-specific, Cre-mediated mutagenesis in mice.Nucleic Acids Res. 1997; 25: 1317-1318
- Osteoblast lineage-specific effects of notch activation in the skeleton.Endocrinology. 2013; 154: 623-634
- Effect of primary and secondary structure of oligodeoxyribonucleotides on the fluorescent properties of conjugated dyes.Nucleic Acids Res. 2002; 30: 2089-2195
- Multiplex quantitative PCR using self-quenched primers labeled with a single fluorophore.Nucleic Acids Res. 2002; 30: e37
- The notch ligand Delta1 recruits Dlg1 at cell-cell contacts and regulates cell migration.J Biol Chem. 2004; 279: 55818-55826
- An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells.Development. 1994; 120: 2421-2430
- Proto-oncogene of int-3, a mouse Notch homologue, is expressed in endothelial cells during early embryogenesis.Genes Cells. 1997; 2: 213-224
- Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system.J Biol Chem. 1992; 267: 21879-21885
- Enzymatic assembly of DNA molecules up to several hundred kilobases.Nat Methods. 2009; 6: 343-345
- Housekeeping and tissue-specific genes in mouse tissues.BMC Genomics. 2007; 8: 127
- Guidelines for assessment of bone microstructure in rodents using micro-computed tomography.J Bone Miner Res. 2010; 25: 1468-1486
- Age-related changes in trabecular architecture differ in female and male C57BL/6J mice.J Bone Miner Res. 2007; 22: 1197-1207
- Generation of Cre recombinase-specific monoclonal antibodies, able to characterize the pattern of Cre expression in cre-transgenic mouse strains.J Immunol Methods. 1997; 207: 203-212
- An antibody to Notch2 reverses the osteopenic phenotype of Hajdu-Cheney mutant male mice.Endocrinology. 2017; 158: 730-742
- ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo.J Exp Med. 2010; 207: 623-635
- Notch signaling and the skeleton.Endocr Rev. 2016; 37: 223-253
- The intracellular domains of Notch1 and Notch2 are functionally equivalent during development and carcinogenesis.Development. 2015; 142: 2452-2463
- Marginal zone B-cells, a gatekeeper of innate immunity.Front Immunol. 2011; 2: 63
- High bone turnover in mice carrying a pathogenic Notch2-mutation causing Hajdu-Cheney syndrome.J Bone Miner Res. 2018; 33: 70-83
Article info
Publication history
Footnotes
Supported by National Institute of Diabetes and Digestive and Kidney Disease grant DK045227 (E.C.) and National Institute of Arthritis and Musculoskeletal and Skin Diseases grants AR063049 (E.C.) and AR068160 (E.C.).
J.Y. and S.Z. contributed equally to this work; A.S. and E.C. contributed equally as senior/corresponding authors to this work.
Disclosures: C.S. and A.N.E. receive stock options from Regeneron Pharmaceuticals.
Identification
Copyright
User license
Elsevier user license |
Permitted
For non-commercial purposes:
- Read, print & download
- Text & data mine
- Translate the article
Not Permitted
- Reuse portions or extracts from the article in other works
- Redistribute or republish the final article
- Sell or re-use for commercial purposes
Elsevier's open access license policy