Investigation of hyaluronan function in the mouse through targeted mutagenesis.
It has become increasingly apparent that the high molecular mass glycosaminoglycan, hyaluronan (HA), is required for many morphogenetic processes during vertebrate development. This renewed understanding of the various developmental roles for HA, has come about largely through the advent of gene targeting approaches in the mouse. To date, mutations have been engineered in the enzymes responsible for biosynthesis and degradation and for those proteins that bind to HA within the extracellular matrix and at the cell surface. Collectively, the phenotypes resulting from these mutations demonstrate that HA is critical for normal mammalian embryogenesis and for various processes in postnatal and adult life (Table 1). In this article we will review our progress in understanding the biological functions for HA through targeted mutagenesis of the HA synthase 2 (Has2) and 3 (Has3) genes. Data that has been obtained from a conventional targeted disruption of the Has2 gene, is presented in an accompanying review by Camenisch and McDonald. More specifically, in this review we will provide an overview of the conditional gene targeting strategy being used to create tissue-specific deficiencies in Has2 function, along with our progress in understanding the role for Has3-dependent HA biosynthesis.
Spicer
Andrew P
AP
Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA. aspicer@ibt.tamu.edu
Tien
Janet Lee
JL
Joo
Adriane
A
Bowling
Rodney A
RA
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D018390:Gene Targeting / Q000379:methods; D014453:Glucuronosyltransferase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis; D010641:Phenotype
D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491099:Has2 protein, mouse; C491356:Has3 protein, mouse; D000076002:Hyaluronan Synthases