Upstream control elements of the proopiomelanocortin gene and their use
AssigneeOregon Health & Science University
InventorsMalcolm J. Low, Marcelo Rubinstein, Flavio Silva Junqueira de Souza
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Abstract
The nucleic acid sequence of the POMC enhancer is disclosed herein. Sequences from the human, rat, rabbit, hamster, mouse, and cow POMC enhancer are disclosed. Hybrid transgenes, comprising a POMC transcriptional control element operably linked to a nucleic acid sequence encoding a marker are also enclosed. In addition, transgenic mice carrying a hybrid transgene including a POMC control element operably linked to a marker are disclosed herein.
Claims43
An isolated proopiomelanocortin enhancer element, comprising a nucleic acid sequence set forth as
- a) SEQ ID NO:
- 9 or at most fifty conserved enhancer substitutions thereof;
- b) SEQ ID NO:
- 15 or at most twenty conserved enhancer substitutions thereof;
- or
- c) SEQ ID NO:
- 19 or at most fifteen conserved enhancer substitutions thereof.
An isolated proopiomelanocortin enhancer element comprising a nucleic acid sequence comprising one or more of
- a) an nPOMC1 element comprising a nucleic acid sequence as set forth as SEQ ID NO:
- 1, SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 4, SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, or a conserved enhancer substitution thereof,
- b) an nPOMC2 element comprising a nucleic acid sequence as set forth as, SEQ ID NO:
- 10, SEQ ID NO:
- 11, SEQ ID NO:
- 12, SEQ ID NO:
- 13, SEQ ID NO:
- 14, SEQ ID NO:
- 15, or a conserved enhancer substitution thereof;
- or
- c) an nPOMC3 element comprising a nucleic acid sequence as set forth as SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18, SEQ ID NO:
- 19 or a conserved enhancer substitution thereof;
- wherein the enhancer element directs expression of a heterologous nucleic acid sequence in a proopiomelanocortin neuron.
An isolated enhancer element comprising a nucleic acid sequence at least 70% homologous to an enhancer element comprising a nucleic acid sequence set forth as SEQ ID NO:
- 1, SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 4, SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 10, SEQ ID NO:
- 11, SEQ ID NO:
- 12, SEQ ID NO:
- 13, or SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18, SEQ ID NO:
- 19
- wherein the enhancer element directs expression of a heterologous nucleic acid sequence in a proopiomelanocortin neuron.
A transgenic mouse expressing a marker in proopiomelanocortin neurons, wherein the mouse comprises a transgene comprising a nucleic acid encoding the marker operably linked to a proopiomelanocortin enhancer sequence, and wherein the proopiomelanocortin enhancer sequence directs expression of the marker in proopiomelanocortin neurons in the arcuate nucleus of the mouse;
- and wherein a section of the arcuate nucleus of the mouse can be used to determine if the agent affects caloric intake, food intake, appetite, or energy expenditure.
Dependencies are inferred from the claim text.