@article{Spaeth:2015:10.1007/s00125-015-3635-3,
author = {Spaeth, JM and Hunter, CS and Bonatakis, L and Guo, M and French, CA and Slack, I and Hara, M and Fisher, SE and Ferrer, J and Morrisey, EE and Stanger, BZ and Stein, R},
doi = {10.1007/s00125-015-3635-3},
journal = {Diabetologia},
pages = {1836--1844},
title = {The FOXP1, FOXP2 and FOXP4 transcription factors are required for islet alpha cell proliferation and function in mice},
url = {http://dx.doi.org/10.1007/s00125-015-3635-3},
volume = {58},
year = {2015}
}

Download

TY  - JOUR
AB  - Aims/hypothesis Several forkhead box (FOX) transcriptionfactor family members have important roles in controllingpancreatic cell fates and maintaining beta cell mass and function,including FOXA1, FOXA2 and FOXM1. In this studywe have examined the importance of FOXP1, FOXP2 andFOXP4 of the FOXP subfamily in islet cell developmentand function.Methods Mice harbouring floxed alleles for Foxp1, Foxp2and Foxp4 were crossed with pan-endocrine Pax6-Cre transgenicmice to generate single and compound Foxp mutantmice. Mice were monitored for changes in glucose toleranceby IPGTT, serum insulin and glucagon levels by radioimmunoassay,and endocrine cell development and proliferation byimmunohistochemistry. Gene expression and glucosestimulatedhormone secretion experiments were performedwith isolated islets.Results Only the triple-compound Foxp1/2/4 conditionalknockout (cKO) mutant had an overt islet phenotype, manifestedphysiologically by hypoglycaemia andhypoglucagonaemia. This resulted from the reduction inglucagon-secreting alpha cell mass and function. The proliferationof alpha cells was profoundly reduced in Foxp1/2/4cKO islets through the effects on mediators of replication (i.e.decreased Ccna2, Ccnb1 and Ccnd2 activators, and increasedCdkn1a inhibitor). Adult islet Foxp1/2/4 cKO beta cells secreteinsulin normally while the remaining alpha cells haveimpaired glucagon secretion.Conclusions/interpretation Collectively, these findings revealan important role for the FOXP1, 2, and 4 proteins ingoverning postnatal alpha cell expansion and function.
AU  - Spaeth,JM
AU  - Hunter,CS
AU  - Bonatakis,L
AU  - Guo,M
AU  - French,CA
AU  - Slack,I
AU  - Hara,M
AU  - Fisher,SE
AU  - Ferrer,J
AU  - Morrisey,EE
AU  - Stanger,BZ
AU  - Stein,R
DO  - 10.1007/s00125-015-3635-3
EP  - 1844
PY  - 2015///
SN  - 1432-0428
SP  - 1836
TI  - The FOXP1, FOXP2 and FOXP4 transcription factors are required for islet alpha cell proliferation and function in mice
T2  - Diabetologia
UR  - http://dx.doi.org/10.1007/s00125-015-3635-3
VL  - 58
ER  - 

Download