Double NF1 inactivation affects adrenocortical function in NF1Prx1 mice and a human patient

PloS One
Karolina KobusMateusz Kolanczyk

Abstract

Neurofibromatosis type I (NF1, MIM#162200) is a relatively frequent genetic condition, which predisposes to tumor formation. Apart from tumors, individuals with NF1 often exhibit endocrine abnormalities such as precocious puberty (2,5-5% of NF1 patients) and some cases of hypertension (16% of NF1 patients). Several cases of adrenal cortex adenomas have been described in NF1 individuals supporting the notion that neurofibromin might play a role in adrenal cortex homeostasis. However, no experimental data were available to prove this hypothesis. We analysed Nf1Prx1 mice and one case of adrenal cortical hyperplasia in a NF1patient. In Nf1Prx1 mice Nf1 is inactivated in the developing limbs, head mesenchyme as well as in the adrenal gland cortex, but not the adrenal medulla or brain. We show that adrenal gland size is increased in NF1Prx1 mice. Nf1Prx1 female mice showed corticosterone and aldosterone overproduction. Molecular analysis of Nf1 deficient adrenals revealed deregulation of multiple proteins, including steroidogenic acute regulatory protein (StAR), a vital mitochondrial factor promoting transfer of cholesterol into steroid making mitochondria. This was associated with a marked upregulation of MAPK pathway and a female s...Continue Reading

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Citations

May 17, 2019·Abdominal Radiology·Ajaykumar C MoraniKhaled M Elsayes
Jul 15, 2017·The British Journal of Radiology·Agrons Michelle MKhaled M Elsayes
Aug 31, 2019·Dermatologic Clinics·Benjamin Becker, Roy E Strowd
Jan 24, 2021·Molecular and Cellular Endocrinology·Ioannis OikonomakosAndreas Schedl

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Methods Mentioned

BETA
PCR
protein assay
electrophoresis
ELISA

Software Mentioned

Decodon
ABI 7900 SDS -
Delta2D
MASCOT

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