Expression of Npc1 in glial cells corrects sterility in Npc1(-/-) mice.
Niemann-Pick type C1 (NPC) disease is an autosomal recessive neurodegenerative disorder. One feature of the mouse model of NPC1 is it's infertility. We have made transgenic mice which express the Npc1 protein exclusively in fibrillary astrocytes, using the glial fibrillary acidic protein (GFAP) promoter. This selective expression of Npc1 corrects sterility in GFAP-Npc1(-/-), Npc1(-/-) mice. Counts of acidophils in the pituitary of GFAP-Npc1E, Npc1(-/-) mice, as compared Npc1(-/-) mice, and measurements of dopamine D2 receptor (DRD2) mRNA in the pituitary, suggest mechanisms for fertility enhancement. We conclude that the correction of sterility in GFAP-Npc1E, Npc1(-/-) mice is a result of restoring hypothalamic control of the pituitary.
Donohue
C
C
Department of Pediatrics, University of Arizona, Tucson, Arizona, USA.
Marion
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S
Erickson
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RP
D000818:Animals; D001483:Base Sequence; D001713:Biphenyl Compounds; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007247:Infertility, Female / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009457:Neuroglia / Q000502:physiology*; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D010053:Ovary / Q000503:physiopathology; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics; D013267:Stilbenes
C445860:4,4'-bis(2-sulfostyryl)biphenyl; D001713:Biphenyl Compounds; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D013267:Stilbenes