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Bill Horton Laboratory

Summary:

We are interested in how bones grow. More precisely, we want to understand the molecular and cellular mechanisms that control mammalian skeletal development, especially those involved in linear bone growth. Skeletal growth is primarily responsible for the final form of adult mammals. This is achieved for most bones through the generation of cartilage models that serve as a templates for bone growth, a process known as endochondral ossification. Once the embryonic bone is formed, endochondral ossification occurs near the ends of bones in so called growth plates .

The growth plate is a dynamic structure with a leading edge where new cells arise through mitosis, intermediate zones where terminally differentiatng cells synthesize matrix and facilitate its maturation into a functional template and a trailing edge where the template is degraded and replaced by bone. The synthesis of template, chondrogenesis, drives this process to a large extent.

A large number of genes must be involved in regulating these events judging from the many inherited human disorders (the chondrodysplasias) manifesting defective bone growth, as well as, the many naturally occurring skeletal mutants in mice and other species. However, there must also be much redundancy considering the many man-made misexpression and knockout mouse mutants that exhibit no abnormalities of skeletal development despite disrupting expression of genes that influence basic cell functions such as mitosis and differentiation. Our goal is to understand what the critical genes are and how they work to control the proliferation, survival and terminal differentiation of growth plate chondrocytes. Our experimental approach utilizes a wide variety of biochemical, molecular genetic, immunologic, molecular biology and cell biology methods. It is hoped our results will provide insight into the fundamental biologic process of growth and also establish a rational basis for new therapies for patients with bone growth disorders.

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Organisms and Viruses

  • B6C3Fe a/a-Glra1spd/J ( Mus musculus )

    The spasmodic mouse strain carries a single point mutation (A52S) in the α1 subunit of the glycine receptor (GlyR).

  • KI Fgfr3KO / TG Col2-pd2GFP ( Mus musculus )

    This strain is homozygous for the Col2-pd2GFP transgene and heterozygous for the Fgfr3 knockout allele.

  • KI Fgfr3TDII ( Mus musculus )

    Knock-in of activating mutation found in thanatophoric dysplasia into Fgfr3 locus.

  • KI Fgfr3TDII / TG Col2-pd2GFP ( Mus musculus )

    Insertion of 2 transgenes consisting of knock-in of activating mutation found in thanatophoric dysplasia into Fgfr3 locus and the Col2 promoter driving GFP.

  • KIFgfr3KO ( Mus musculus )

    This knockout strain is the result of a targeted disruption in Fgfr3.

  • Scx-GFP mice ( Mus musculus )

    Congenital Limb Deformities

  • TG Col2-GFP ( Mus musculus )

    Insertion of transgene consisting of the Col2 promoter driving expression of GFP.

  • TG Col2-pd2GFP ( Mus musculus )

    Insertion of transgene consisting of the Col2 promoter driving expression of pd2GFP, a less stable form of GFP.

  • Tg Fgfr3 AC-CH ( Mus musculus )

    Insertion of a BAC transgene containing Fgfr3 harboring the achondroplasia mutation and tagged with cherry fluorescent protein.

    The Fgfr3 BAC transgene was prepared by Gene Bridges (Heidelberg, Germany). The mouse strain was generated by the Transgenic Animal Facility at the University of Michigan.

  • Tg Fgfr3 CR-CE ( Mus musculus )

    Insertion of a BAC transgene harboring a cleavage resistant form of Fgfr3 tagged with cerulean fluorescent protein

    The Fgfr3 BAC transgene was prepared by Gene Bridges (Heidelberg, Germany). The mouse strain was generated by the Transgenic Animal Facility at the University of Michigan.

  • Tg Fgfr3 WT-VE ( Mus musculus )

    Insertion of a BAC transgene containing WT Fgfr3 tagged with venus fluorescent protein.

    The Fgfr3 BAC transgene was prepared by Gene Bridges (Heidelberg, Germany). The mouse strain was generated by the Transgenic Animal Facility at the University of Michigan.

  • TGActin-CHIP ( Mus musculus )

    Mice carry a transgene consisting of the β-actin promoter driving expression of CHIP.


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Last updated: 2013-01-29T21:24:23.735-06:00

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The eagle-i Consortium is supported by NIH Grant #5U24RR029825-02 / Copyright 2016