Nestin-Cre mice are affected by hypopituitarism, which is not due to significant activity of the transgene in the pituitary gland.
Nestin-Cre mice express Cre recombinase under control of the rat nestin promoter and central nervous system (CNS) enhancer. While endogenous Nestin is expressed in some other tissues including the pituitary gland, Nestin-Cre mice induce recombination predominantly in the CNS. For this reason, they have been widely used to explore gene function or cell fate in the latter. Pituitary hormonal deficiencies, or hypopituitarism, are associated with a wide range of symptoms and with a significant morbidity. These can have a neural and/or a pituitary origin as the gland's secretions are controlled by the hypothalamus. We report here that Nestin-Cre mice themselves are affected by mild hypopituitarism. Hence, physiological consequences are expected, especially in combination with defects resulting from Cre mediated deletion of any gene under investigation. To further investigate the origin of this phenotype, we re-examined the activity of the transgene. We compared it with expression of Nestin itself in the context of the hypothalamo-pituitary axis, especially in the light of a recent report showing pituitary Nestin-Cre activity, which contrasts with previous data. Our results disagree with those of this recent study and do not support the claim that Nestin positive cells are present in the pituitary anlagen, the Rathke's pouch (RP). Moreover we did not observe any significant activity in the post-natal pituitary, in agreement with the initial report.
Galichet
Christophe
C
Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, London, United Kingdom.
Lovell-Badge
Robin
R
Rizzoti
Karine
K
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D007018:Hypopituitarism / Q000235:genetics / Q000378:metabolism*; D019426:Integrases / Q000235:genetics* / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D064231:Nestin; D010902:Pituitary Gland / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D013972:Thyrotropin / Q000378:metabolism; D019076:Transgenes / Q000235:genetics / Q000502:physiology*
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D013972:Thyrotropin; D013006:Growth Hormone; C045073:Cre recombinase; D019426:Integrases