Transgenic Mice Expressing Lipoprotein Lipase in Adipose Tissue

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and adipocyte metabolism. Defects in LPL can lead to hypertriglyceridemia and the subsequent development of atherosclerosis. The mechanisms of regulation of this enzyme are complex and may occur at multiple levels of gene expression. Because the 3′-untranslated region (UTR) is involved in LPL translational regulation, transgenic mice were generated with adipose tissue expression of an LPL construct either with or without the proximal 3′-UTR and driven by the transgenic were and the in a in LPL in adipose in of and the mice with an expression in the mice without the proximal in the of of and LPL the 3′-UTR of LPL the of and the of the 3′-UTR in a in a of adipose LPL Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and adipocyte metabolism. Defects in LPL can lead to hypertriglyceridemia and the subsequent development of atherosclerosis. The mechanisms of regulation of this enzyme are complex and may occur at multiple levels of gene expression. Because the 3′-untranslated region (UTR) is involved in LPL translational regulation, transgenic mice were generated with adipose tissue expression of an LPL construct either with or without the proximal 3′-UTR and driven by the transgenic were and the in a in LPL in adipose in of and the mice with an expression in the mice without the proximal in the of of and LPL the 3′-UTR of LPL the of and the of the 3′-UTR in a in a of adipose LPL Lipoprotein lipase (LPL) lipoprotein adipose adipose lipoprotein adipose adipose is a enzyme in metabolism. The enzyme is and by and and to the of the of and the in LPL with Lipoprotein the of LPL regulation is complex and at levels of and in to and translational regulation of to and were in LPL with in adipocyte LPL the in LPL in and is to LPL is an of adipocyte and LPL expression in with in adipose tissue can are of LPL of the and in the development of an adipocyte transgenic mice LPL were in adipose and LPL were in of LPL with LPL mice hypertriglyceridemia and adipose tissue the a of hypertriglyceridemia of LPL LPL the mice by and a subsequent and a to mice the mice were with LPL expression in or The LPL in a of the the of LPL in LPL in the LPL with hypertriglyceridemia and to the LPL in adipose tissue this generated transgenic mice LPL in adipose of to the of the of 3′-untranslated in were construct the 3′-UTR of the LPL the transgenic construct the proximal mice and the in adipose LPL to the of the LPL by the transgenic in mice without the proximal the levels of transgenic the levels of transgenic Because the 3′-UTR is by are are with the expression of a LPL to the of of the and of LPL with or without the proximal 3′-UTR of the LPL were were the of the the of a LPL the the to a LPL the of the the a and of the 3′-UTR with the of the region were to the the of The the of the the and the to and and the transgenic mice a LPL gene in the proximal 3′-untranslated region in adipose of The region of with the LPL and The region of and the with of and a the construct to the a The 3′-UTR of at and of the LPL with and were in the The with and and to the in The of the construct and and to the in The with the and and this and in the by mice were to the of the the LPL mice were at the of at the of and the of the and the of to of the were to and transgenic were were and were at of either a or and at were mice were a and were by of to the the to of the and the to in the to an the the a of the were and were of of to with by and to the with a by of were with and and the with a of the in were of of were a and with a of of the The LPL with a The the and with a the of of of and to the the to of the and the to of the of the the were of the were a and an or in the or the were and were were with of and were with to adipose tissue were by and to were with at a of and with at a of by with an of LPL and LPL were in mice and to LPL of adipose tissue in of at the tissue LPL in The LPL an and the of the LPL were with of of the and transgenic mice by a and and levels were with and were the the of were and were the of a were and and of LPL in a with The and the were in and The were the to by with a were by the without and the were by and the were the at the and the LPL in to transgenic mice are in the the and the of The construct in the 3′-untranslated region with and an transgenic LPL construct to the and the of an were generated a construct the and mice transgenic of the transgenic to transgenic The construct the an and the proximal The construct is is and the are in and enzyme are of The in the the The region the were transgenic or a of mice with a to and LPL levels of in the the mice were a or in the in a and the mice in and were in gene were in the mice with a of LPL adipose and were with to either or in the in transgenic and in the in and transgenic expression in adipose and of and with with a LPL and with an the adipose adipose adipose the proximal the of expression the with to and the of and of expression of and in in and in The of and in and at levels in transgenic and the in transgenic mice and at levels with the gene in the of and transgenic the of LPL in the to the of the transgenic expression in the and in transgenic and of transgenic and mice and to at to of the is and and of of were to of of and were is of with a of levels of LPL in transgenic and of and were to LPL levels in transgenic and levels LPL the of LPL in of the LPL in were levels of LPL LPL in of transgenic and mice the a in in of and an in in adipose tissue a the in of mice to the expression of the a in LPL this in the this in to the expression this in with expression of the in mice were or in and LPL in adipose tissue and a with the with in by levels of levels adipose mice were with to expression levels of with LPL in in transgenic or LPL in tissue of transgenic in and in the and of an LPL with the of in LPL in a of with and were in of in with expression levels of in transgenic in and transgenic and of in the and the of in of tissue mice in were and with to the were the with and were adipose tissue LPL in in in or were in with and to lipoprotein in were in the of the or and in lipase and in transgenic and in a of transgenic transgenic mice and mice were by were and and LPL in in and levels of LPL in an in or in transgenic may by in mice either a or a a in in either mice or in mice a a transgenic and mice in transgenic mice and were in and transgenic and mice and transgenic and transgenic and mice or of of mice transgenic mice mice and transgenic mice a of the of the in the mice were the of transgenic and mice either or were and were and are the mice in were in the by and Because the construct the 3′-UTR this to the of LPL of and the of the in the in the the in and in the expression of the and were and with either or in mice and this in LPL by the in the LPL of LPL with mice were and with by and in mice LPL mice this in LPL to the and mice were with and with and with to LPL by and in mice with the mice of LPL with and with levels of levels of to expression of in transgenic of adipose tissue either mice or mice were by to and with either an or a the the and of either or mice were with and with and a of and and mice were with and with to the and The of this with and the and the were a of transgenic the mice expression of in to the in in the the mice in and in LPL and LPL with a of expression the with the the of LPL in the transgenic and in and LPL and in the of transgenic and and to or in the of the translational regulation of generated transgenic were driven by the and and in the or of the proximal 3′-UTR to of transgenic mice with or this is the of transgenic mice LPL in adipose mice with either construct expression levels of and LPL in the LPL expression in this in the The this in expression is the expression and the of the proximal 3′-UTR in expression of the LPL in is levels of LPL or in in were either the were either or are this of in the may in or LPL may to a of LPL in an in to an in in adipose or may or LPL and adipose tissue LPL adipose tissue LPL and in LPL in and in of in LPL may the in the adipose enzyme in and transgenic the of and the the the by and the were with LPL in and were at the to expression. in the the proximal a LPL and LPL expression. The by of LPL were by at levels in and transgenic mice the at expression of to LPL in transgenic mice with the of and and by the the of and the in mice the of transgenic and a in the of the of the the of LPL in an LPL and this is in the of and the of adipose tissue of or Lipoprotein in this regulation is the of the of the 3′-UTR of LPL and at the of mice LPL in adipose tissue with the construct to LPL of is to the of the 3′-UTR of the in LPL is by and to the of an with the of the 3′-UTR and are and a translational of LPL the of the proximal 3′-UTR to this translational in an LPL is in 3′-UTR is can involved in translational and is by a and is by the of a to a the 3′-UTR may a complex of the 3′-UTR with the or the in and regulation by The of the is involved with regulation is transgenic may of the of of the this of to levels of the 3′-UTR to transgenic LPL in adipose in the of the proximal 3′-UTR of with transgenic mice the the levels of are the levels of The 3′-UTR is by and are with the expression of a LPL to the of of the and with to the levels of transgenic mice may LPL translational regulation in and the of the 3′-UTR of LPL in Lipoprotein lipase (LPL) lipoprotein adipose adipose lipoprotein adipose adipose is a enzyme in metabolism. The enzyme is and by and and to the of the of and the in LPL with Lipoprotein the of LPL regulation is complex and at levels of and in to and translational regulation of to and were in LPL with in adipocyte LPL the in LPL in and is to LPL LPL is an of adipocyte and LPL expression in with in adipose tissue can are of LPL of the and in the development of an adipocyte transgenic mice LPL were in adipose and LPL were in of LPL with LPL mice hypertriglyceridemia and adipose tissue the a of hypertriglyceridemia of LPL LPL the mice by and a subsequent and a to mice the mice were with LPL expression in or The LPL in a of the the of LPL in LPL in the LPL with hypertriglyceridemia and to the LPL in adipose tissue this generated transgenic mice LPL in adipose of to the of the of 3′-untranslated in were construct the 3′-UTR of the LPL the transgenic construct the proximal mice and the in adipose LPL to the of the LPL by the transgenic in mice without the proximal the levels of transgenic the levels of transgenic Because the 3′-UTR is by are are with the expression of a LPL to the of of the and of LPL with or without the proximal 3′-UTR of the LPL were were the of the the of a LPL the the to a LPL the of the the a and of the 3′-UTR with the of the region were to the the of The the of the the and the to and and the transgenic mice a LPL gene in the proximal 3′-untranslated region in adipose of The region of with the LPL and The region of and the with of and a the construct to the a The 3′-UTR of at and of the LPL with and were in the The with and and to the in The of the construct and and to the in The with the and and this and in the by mice were to the of the the LPL mice were at the of at the of and the of the and the of to of the were to and transgenic were were and were at of either a or and at were mice were a and were by of to the the to of the and the to in the to an the the a of the were and were of of to with by and to the with a by of were with and and the with a of the in were of of were a and with a of of the The LPL with a The the and with a the of of of and to the the to of the and the to of the of the the were of the were a and an or in the or the were and were were with of and were with to adipose tissue were by and to were with at a of and with at a of by with an of LPL and LPL were in mice and to LPL of adipose tissue in of at the tissue LPL in The LPL an and the of the LPL were with of of the and transgenic mice by a and and levels were with and were the the of were and were the of a were and and of LPL in a with The and the were in and The were the to by with a were by the without and the were by and the were the at the and the and of LPL with or without the proximal 3′-UTR of the LPL were were the of the the of a LPL the the to a LPL the of the the a and of the 3′-UTR with the of the region were to the the of The the of the the and the to and and the transgenic mice a LPL gene in the proximal 3′-untranslated region in adipose of The region of with the LPL and The region of and the with of and a the construct to the a The 3′-UTR of at and of the LPL with and were in the The with and and to the in The of the construct and and to the in The with the and and this and in the by mice were to the of the the LPL mice were at the of at the of and the of the and the of to of the were to and transgenic were were and were at of either a or and at were mice were a and were by of to the the to of the and the to in the to an the the a of the were and were of of to with by and to the with a by of were with and and the with a of the in were of of were a and with a of of the The LPL with a The the and with a the of of of and to the the to of the and the to of the of the the were of the were a and an or in the or the were and were were with of and were with to adipose tissue were by and to were with at a of and with at a of by with an of LPL and LPL were in mice and to LPL of adipose tissue in of at the tissue LPL in The LPL an and the of the LPL were with of of the and transgenic mice by a and and levels were with and were the the of Lipoprotein were and were the of a were and and LPL of LPL in a with The and the were in and The were the to by with a were by the without and the were by and the were the at the and the LPL in to transgenic mice are in the the and the of The construct in the 3′-untranslated region with and an transgenic LPL construct to the and the of an were generated a construct the and mice were transgenic or a of mice with a to and LPL levels of in the the mice were a or in the in a and the mice in and were in gene were in the mice with a of LPL adipose and were with to either or in the in transgenic and in the in and transgenic expression in adipose and of and with with a LPL and with an the adipose adipose adipose the proximal the of expression the with to and the of and of expression of and in in and in The of and in and at levels in transgenic and the in transgenic mice and at levels with the gene in the of and transgenic the of LPL in the to the of the transgenic expression in the and in transgenic and of transgenic and mice and to at to of the is and and of of were to of of and were is of with a of levels of LPL in transgenic and of and were to LPL levels in transgenic and levels LPL the of LPL in of the LPL in were levels of LPL LPL in of transgenic and mice the a in in of and an in in adipose tissue a the in of mice to the expression of the a in LPL this in the this in to the expression this in with expression of the in mice were or in and LPL in adipose tissue and a with the with in by levels of levels adipose mice were with to expression levels of with LPL in in transgenic or LPL in tissue of transgenic in and in the and of an LPL with the of in LPL in a of with and were in of in with expression levels of in transgenic in and transgenic and of in the and the of in of tissue mice in were and with to the were the with and were adipose tissue LPL in in in or were in with and to lipoprotein in were in the of the or and in lipase and in transgenic and in a of transgenic transgenic mice and mice were by were and and LPL in in and levels of LPL in an in or in transgenic may by in mice either a or a a in in either mice or in mice a a transgenic and mice in transgenic mice and were in and transgenic and mice and transgenic and transgenic and mice or of of mice transgenic mice mice and transgenic mice a of the of the in the mice were the of transgenic and mice either or were and were and are the mice in were in the by and Because the construct the 3′-UTR this to the of LPL of and the of the in the in the the in and in the expression of the and were and with either or in mice and this in LPL by the in the LPL of LPL with mice were and with by and in mice LPL mice this in LPL to the and mice were with and with and with to LPL by and in mice with the mice of LPL with and with levels of levels of to expression of in transgenic of adipose tissue either mice or mice were by to and with either an or a the the and of either or mice were with and with and a of and and mice were with and with to the and The of this with and the and the were a of transgenic the mice expression of in to the in in the the mice in and in LPL and LPL with a of expression the with the the of LPL in the transgenic and in and LPL and in the of transgenic and and to or in LPL in to transgenic mice are in the the and the of The construct in the 3′-untranslated region with and an transgenic LPL construct to the and the of an were generated a construct the and mice were transgenic or a of mice with a to and LPL levels of in the the mice were a or in the in a and the mice in and were in gene were in the mice with a of LPL adipose and were with to either or in the in transgenic and in the in and transgenic the proximal the of expression the with to and the of and of expression of and in in and in The of and in and at levels in transgenic and the in transgenic mice and at levels with the gene in the of and transgenic the of LPL in the to the of the transgenic of the LPL in were levels of LPL LPL in of transgenic and mice the a in in of and an in in adipose tissue a the in of mice to the expression of the a in LPL this in the this in to the expression this in with expression of the in mice were or in and LPL in adipose tissue and a with the with in by levels of levels adipose mice were with to expression levels of with LPL in were the with and were adipose tissue LPL in in in or were in with and to lipoprotein in were in the of the or and in LPL in in and levels of LPL in an in or in transgenic may by in mice either a or a a in in either mice or in mice a a transgenic and mice in transgenic mice and were in and transgenic and mice by and Because the construct the 3′-UTR this to the of LPL of and the of the in the in the the in and in the expression of the and were and with either or in mice and this in LPL by the in the LPL of LPL with mice were and with by and in mice LPL mice this in LPL to the and mice were with and with and with to LPL by and in mice with the mice of LPL with and with of transgenic the mice expression of in to the in in the the mice in and in LPL and LPL with a of expression the with the the of LPL in the transgenic the of the translational regulation of generated transgenic were driven by the and and in the or of the proximal 3′-UTR to of transgenic mice with or this is the of transgenic mice LPL in adipose mice with either construct expression levels of and LPL in the LPL expression in this in the The this in expression is the expression and the of the proximal 3′-UTR in expression of the LPL in is levels of LPL or in in were either the were either or are this of in the may in or LPL may to a of LPL in an in to an in in adipose or may or LPL and adipose tissue LPL adipose tissue LPL and in LPL in and in of in LPL may the in the adipose enzyme in and transgenic the of and the the the by and the were with LPL in and were at the to expression. in the the proximal a LPL and LPL expression. The by of LPL were by at levels in and transgenic mice the at expression of to LPL in transgenic mice with the of and and by the the of and the in mice the of transgenic and a in the of the of the the of LPL in an LPL and this is in the of and the of adipose tissue of or Lipoprotein in this regulation is the of the of the 3′-UTR of LPL and at the of mice LPL in adipose tissue with the construct to LPL of is to the of the 3′-UTR of the in LPL is by and to the of an with the of the 3′-UTR and are and a translational of LPL the of the proximal 3′-UTR to this translational in an LPL is in 3′-UTR is can involved in translational and is by a and is by the of a to a the 3′-UTR may a complex of the 3′-UTR with the or the in and regulation by The of the is involved with regulation is transgenic may of the of of the this of to levels of the 3′-UTR to transgenic LPL in adipose in the of the proximal 3′-UTR of with transgenic mice the the levels of are the levels of The 3′-UTR is by and are with the expression of a LPL to the of of the and with to the levels of transgenic mice may LPL translational regulation in and the of the 3′-UTR of LPL in the of the translational regulation of generated transgenic were driven by the and and in the or of the proximal 3′-UTR to of transgenic mice with or this is the of transgenic mice LPL in adipose mice with either construct expression levels of and LPL in the LPL expression in this in the The this in expression is the expression and the of the proximal 3′-UTR in expression of the LPL in is levels of LPL or in in were either the were either or are this of in the may in or LPL may to a of LPL in an in to an in in adipose or may or LPL and adipose tissue LPL adipose tissue LPL and in LPL in and in of in LPL may the in the adipose enzyme in and transgenic the of and the the the by and the were with LPL in and were at the to expression. in the the proximal a LPL and LPL expression. The by of LPL were by at levels in and transgenic mice the at expression of to LPL in transgenic mice with the of and and by the the of and the in mice the of transgenic and a in the of the of the the of LPL in an LPL and this is in the of and the of adipose tissue of or Lipoprotein in this regulation is the of the of the 3′-UTR of LPL and at the of mice LPL in adipose tissue with the construct to LPL of is to the of the 3′-UTR of the in LPL is by and to the of an with the of the 3′-UTR and are and a translational of LPL the of the proximal 3′-UTR to this translational in an LPL is in The 3′-UTR is can involved in translational and is by a and is by the of a to a the 3′-UTR may a complex of the 3′-UTR with the or the in and regulation by The of the is involved with regulation is transgenic may of the of of the this of to levels of the 3′-UTR to transgenic LPL in adipose in the of the proximal 3′-UTR of with transgenic mice the the levels of are the levels of The 3′-UTR is by and are with the expression of a LPL to the of of the and with to the levels of transgenic mice may LPL translational regulation in and the of the 3′-UTR of LPL in and in the and