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

Autor: Anu Jalanko, Susann Karlberg, Niklas Karlberg, Matti Jauhiainen, J. Kalervo Hiltunen, Kirsi Sainio, Anna-Elina Lehesjoki, Riikka H. Hämäläinen, Teija T. Toivonen, Natalia Kulesskaya, Marita Lipsanen-Nyman, Vootele Voikar, Kaisa Kettunen, Jorma Toppari, Elina Ikonen, Hannu Jalanko, Maarit Hölttä-Vuori, Riitta Karikoski, Vasily D. Antonenkov
Přispěvatelé: Institute for Molecular Medicine Finland, Neuroscience Center, Research Programme for Molecular Neurology, Research Programs Unit, Heikki Rauvala Research Group, Medicum, Department of Anatomy, Lipid Trafficking Lab, Department of Biochemistry and Developmental Biology, Clinicum, Children's Hospital, Endokrinologian yksikkö, Lastentautien yksikkö, Anna-Elina Lehesjoki / Principal Investigator, HUS Children and Adolescents
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Mulibrey nanism
medicine.medical_specialty
COILED-COIL PROTEIN
QH301-705.5
Cardiomyopathy
Science
LUTEINIZING-HORMONE
BIOGENESIS
Congenic
Biology
medicine.disease_cause
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
FINGER PROTEIN TRIM37
0302 clinical medicine
MOUSE MODELS
Internal medicine
Fatty liver
medicine
Biology (General)
WILMS-TUMOR
Testosterone
ENZYME DEFICIENCIES
Growth failure
LIPID HOMEOSTASIS
ta1184
3112 Neurosciences
medicine.disease
3. Good health
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Infertility
3121 General medicine
internal medicine and other clinical medicine
Tumorigenesis
RAT
3111 Biomedicine
General Agricultural and Biological Sciences
Carcinogenesis
Luteinizing hormone
PEROXISOMES
030217 neurology & neurosurgery
Germ cell
Hormone
Research Article
Zdroj: Biology Open, Vol 5, Iss 5, Pp 584-595 (2016)
Biology Open
ISSN: 2046-6390
Popis: 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 wild-type. 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.
Summary: A congenic Trim37-deficient mouse model recapitulates several features of the human disorder Mulibrey nanism, and thus provides a good model to study disease pathogenesis related to TRIM37 deficiency.
Databáze: OpenAIRE
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