Novel Reporter Alleles of GSK-3 alpha and GSK-3 beta

TY - JOUR

T1 - Novel Reporter Alleles of GSK-3 alpha and GSK-3 beta

AU - Barrell, William B.

AU - Szabo-Rogers, Heather L.

AU - Liu, Karen J.

PY - 2012/11/21

Y1 - 2012/11/21

N2 - Glycogen Synthase Kinase 3 (GSK-3) is a key player in development, physiology and disease. Because of this, GSK-3 inhibitors are increasingly being explored for a variety of applications. In addition most analyses focus on GSK-3 beta and overlook the closely related protein GSK-3 alpha. Here, we describe novel GSK-3 alpha and GSK-3 beta mouse alleles that allow us to visualise expression of their respective mRNAs by tracking beta-galactosidase activity. We used these new lacZ alleles to compare expression in the palate and cranial sutures and found that there was indeed differential expression. Furthermore, both are loss of function alleles and can be used to generate homozygous mutant mice; in addition, excision of the lacZ cassette from GSK-3 alpha creates a Cre-dependent tissue-specific knockout. As expected, GSK3 alpha mutants were viable, while GSK3 beta mutants died after birth with a complete cleft palate. We also assessed the GSK-3 alpha mutants for cranial and sternal phenotypes and found that they were essentially normal. Finally, we observed gestational lethality in compound GSK-3 beta(-/-); GSK3 alpha(+/-) mutants, suggesting that GSK-3 dosage is critical during embryonic development.

AB - Glycogen Synthase Kinase 3 (GSK-3) is a key player in development, physiology and disease. Because of this, GSK-3 inhibitors are increasingly being explored for a variety of applications. In addition most analyses focus on GSK-3 beta and overlook the closely related protein GSK-3 alpha. Here, we describe novel GSK-3 alpha and GSK-3 beta mouse alleles that allow us to visualise expression of their respective mRNAs by tracking beta-galactosidase activity. We used these new lacZ alleles to compare expression in the palate and cranial sutures and found that there was indeed differential expression. Furthermore, both are loss of function alleles and can be used to generate homozygous mutant mice; in addition, excision of the lacZ cassette from GSK-3 alpha creates a Cre-dependent tissue-specific knockout. As expected, GSK3 alpha mutants were viable, while GSK3 beta mutants died after birth with a complete cleft palate. We also assessed the GSK-3 alpha mutants for cranial and sternal phenotypes and found that they were essentially normal. Finally, we observed gestational lethality in compound GSK-3 beta(-/-); GSK3 alpha(+/-) mutants, suggesting that GSK-3 dosage is critical during embryonic development.

KW - INSULIN

KW - ISOFORMS

KW - SECONDARY

KW - SKELETAL-MUSCLE

KW - TISSUE

KW - GLYCOGEN-SYNTHASE KINASE-3

KW - RECOMBINASE

KW - MICE

KW - EXPRESSION

KW - PALATE

U2 - 10.1371/journal.pone.0050422

DO - 10.1371/journal.pone.0050422

M3 - Article

SN - 1932-6203

VL - 7

JO - PL o S One

JF - PL o S One

IS - 11

M1 - 50422

ER -