Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism

Show full item record



Permalink

http://hdl.handle.net/10138/164644

Citation

Kettunen , K M , Karikoski , R , Hamalainen , R H , Toivonen , T T , Antonenkov , V D , Kulesskaya , N , Voikar , V , Holtta-Vuori , M , Ikonen , E , Sainio , K , Jalanko , A , Karlberg , S , Karlberg , N , Lipsanen-Nyman , M , Toppari , J , Jauhiainen , M , Hiltunen , J K , Jalanko , H & Lehesjoki , A-E 2016 , ' Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism ' , Biology open , vol. 5 , no. 5 , pp. 584-595 . https://doi.org/10.1242/bio.016246

Title: Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism
Author: Kettunen, Kaisa M.; Karikoski, Riitta; Hamalainen, Riikka H.; Toivonen, Teija T.; Antonenkov, Vasily D.; Kulesskaya, Natalia; Voikar, Vootele; Holtta-Vuori, Maarit; Ikonen, Elina; Sainio, Kirsi; Jalanko, Anu; Karlberg, Susann; Karlberg, Niklas; Lipsanen-Nyman, Marita; Toppari, Jorma; Jauhiainen, Matti; Hiltunen, J. Kalervo; Jalanko, Hannu; Lehesjoki, Anna-Elina
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Children's Hospital
University of Helsinki, Neuroscience Center
Date: 2016-05-15
Language: eng
Number of pages: 12
Belongs to series: Biology open
ISSN: 2046-6390
URI: http://hdl.handle.net/10138/164644
Abstract: Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37(-/-)) model for MUL. Trim37(-/-) mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37(-/-) mice as compared with wildtype. Both male and female Trim37(-/-) mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37(-/-) mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37(-/-) mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37(-/-) mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37(-/-) mice. The most consistently seen phenotypes in Trim37(-/-) mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37(-/-) mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis.
Subject: Mulibrey nanism
Infertility
Fatty liver
Cardiomyopathy
Tumorigenesis
Growth failure
FINGER PROTEIN TRIM37
COILED-COIL PROTEIN
WILMS-TUMOR
LUTEINIZING-HORMONE
ENZYME DEFICIENCIES
LIPID HOMEOSTASIS
MOUSE MODELS
RAT
PEROXISOMES
BIOGENESIS
3111 Biomedicine
3112 Neurosciences
3121 General medicine, internal medicine and other clinical medicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
584.full.pdf 2.104Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record