EnamelBase: Projects
Ameloblast Differentiation and Amelogenesis: Next-Generation Models to Define Key Mechanisms and Factors Involved in Biological Enamel Formation (Diekwisch Laboratory, URMC)
Personnel: Tom Diekwisch (PI), Xianghong Luan, Mirali Pandya and Connie Tillberg
In the context of the project entitled Ameloblast Differentiation and Amelogenesis: Next-Generation Models to Define Key Mechanisms and Factors Involved in Biological Enamel Formation the URMC team (formerly at Texas A&M University, TAMU) focuses on the role of the vesicle coat protein clathrin in amelogenesis.
Data sets associated with this project are currently being generated.
Cre Mouse Models to Study Amelogenesis (Paine Laboratory, USC)
Personnel: Michael Paine (PI), Rucha Arun Bapat, Yanbin Ji, Joseph Hacia and Yan Zhou
In the context of the project entitled Cre Mouse Models to Study Amelogenesis the USC team addresses the lack of enamel-organ specific Cre-driver lines. Historically, many animal models of amelogenesis relied on the keratin 14-Cre (Krt14-Cre) driver line despite the significant disadvantage that Krt14 is expressed in many tissues. Crossing the Krt14-Cre mouse with a floxed mouse thus often results in multiple organ failure and can severely compromise experiments. Here, we focus on generating mouse models where Cre-recombinase has been knocked into the ameloblastin gene locus for expression in secretory stage ameloblasts (Ambn-Cre) and into the odontogenic ameloblast-associated gene locus for expression in maturation stage ameloblasts (Odam-Cre).
Data sets associated with this project are currently being generated.
Development and Validation of Novel Amelogenesis Models (Hu Laboratory, Univ of Michigan)
Personnel: Jan Hu (PI) and Jim Simmer
In the context of the project entitled Development and Validation of Novel Amelogenesis Models the UM team focuses on the secretory stage of amelogenesis where enamel mineral ribbons initiate on dentin mineral and elongate until the enamel layer reaches its final dimensions. Defects in genes necessary for the secretory stage typically cause thinner (hypoplastic) enamel with a rough surface. Specifically, we take a close look ODAPH (formerly C4orf26), a secreted enamel matrix protein that has not yet been characterized, and 2 secretory-stage ion transporters: the bicarbonate transporter SLC4A4 (NCBe1) and the citrate transporter SLC13A5. Data sets associated with this project currently include:
Enamel Atlas: Systems-level Amelogenesis Tools at Multiple Scales (Joester Laboratory, NU, and Klein Laboratory, UCSF)
Personnel:
- Northwestern University: Derk Joester (PI), Keith Alvares, Stuart Stock, Victoria Cooley and Sarah Boyer
- UCSF: Ophir Klein (PI), Jeff Bush (co-I), Tomas Wald, Adya Verma, Pauline Marangoni, Oscar Cazares, Evelyn Sandoval and David Sung
In the context of the project entitled Enamel Atlas: Systems-level Amelogenesis Tools at Multiple Scales the UCSF/NU team has already generated or will generate:
-
a) constitutively active (Cre) and inducible (CreERT2) Cre recombinase driver lines specific for pre-secretory-, secretory- (AMBN-Cre/CreERT2 andAMELX- Cre; AMELX-CreERT2), and maturation-stage (KLK4-Cre/CreERT2) ameloblasts.
-
b) reporter models for pre-secretory-, secretory- (AMBN-p2A-EGFP), and maturation-stage (KLK4- mCherry) ameloblasts.
-
c) models in which key alleles are flanked by loxP recombination sites (“floxed”), including: MMP20-flox, KLK4-flox, AMTN-flox, AMELX-flox, ENAM-flox, AMBN-flox, and ODAM-flox.
-
d) targeted mutant models of enamel matrix proteins for study of protein-protein interaction sites (AMELX-E3-YLF/GGG, AMELX-E5-YYF/GGG, and AMBN-A254_Y255insX).
Data sets associated with this project currently include: