Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.1 (
alkaline phosphatase
)
47,916
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
DNA methylation is a major mode of epigenetic regulation in the mammalian genome and is essential for embryonic development. The three catalytic DNA methyltransferases (Dnmts), Dnmt1, Dnmt3a, and Dnmt3b, catalyze the methylation of cytosine. Dnmt3b is highly expressed in chondrocytes and global knockout of Dnmt3b led to skeletal deformations and embryonic lethality, suggesting an essential role of Dnmt3b in endochondral bone formation. To further define the role of Dnmt3b in skeletal development, Dnmt3b was deleted in Col2 positive chondrocyte lineage cells. Both axial and appendicular skeletal size were reduced and bone mineralization was delayed in Col2Cre
+
;Dnmt3b
f/f
(Dnmt3b
Col2
) mice at
E14
.5 and E18.5. While Alcian Blue Hematoxylin/Orange G (ABH/OG) staining showed normal chondrocyte columns in control growth plates, the length of hypertrophic chondrocyte zone and type X collagen expression were decreased in E18.5 growth plates from Dnmt3b
Col2
mice. TUNEL and PCNA staining demonstrated that the delay in chondrocyte maturation observed in the Dnmt3b
Col
2
growth plates was not secondary to altered chondrocyte apoptosis or proliferation. Complementary in vitro experiments were performed on primary sternal chondrocytes isolated from control and Dnmt3b
Col2
mice. Gene expression studies confirmed delayed terminal maturation as Mmp13 and Col10a1 expression was down-regulated in Dnmt3b
Col2
chondrocytes. In addition,
alkaline phosphatase
(
ALP
) and Alizarin Red staining confirmed that Dnmt3b deletion in chondrocytes delays in vitro chondrocyte hypertrophic differentiation and matrix mineralization. Mechanistically, Dnmt3b gene deletion resulted in decreased BMP signaling through reduction of Smad1 phosphorylation. These findings show that epigenetic factor, Dnmt3b is necessary for normal chondrocyte hypertrophic maturation and limb development.
...
PMID:Ablation of Dnmt3b in chondrocytes suppresses cell maturation during embryonic development. 2963 97
Embryonic stem cells (ESCs) derived from outbred mice which share several genetic characteristics similar to humans have been requested for developing stem cell-based bioengineering techniques directly applicable to humans. Here, we report the generation of ESCs derived from the inner cell mass of blastocysts retrieved from 9-week-old female outbred ICR mice mated with 9-week-old male outbred ICR mice (
ICR
ESCs). Similar to those from 129/Ola mouse blastocysts (
E14
ESCs), the established
ICR
ESCs showed inherent characteristics of ESCs except for partial and weak protein expression and activity of
alkaline phosphatase
. Moreover,
ICR
ESCs were not originated from embryonic germ cells or pluripotent cells that may co-exist in outbred ICR strain-derived mouse embryonic fibroblasts (
ICR
MEFs) used for deriving colonies from inner cell mass of outbred ICR mouse blastocysts. Furthermore, instead of outbred
ICR
MEFs, hybrid
B6CBAF1
MEFs as feeder cells could sufficiently support
in vitro
maintenance of
ICR
ESC self-renewal. Additionally,
ICR
ESC-specific characteristics (self-renewal, pluripotency, and chromosomal normality) were observed in
ICR
ESCs cultured for 40th subpassages (164 days) on
B6CBAF1
MEFs without any alterations. These results confirmed the successful establishment of ESCs derived from outbred ICR mice, and indicated that self-renewal and pluripotency of the established
ICR
ESCs could be maintained on
B6CBAF1
MEFs in culture.
...
PMID:Generation of embryonic stem cells derived from the inner cell mass of blastocysts of outbred ICR mice. 3248 88
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