Modeling partial monosomy for human chromosome 21q11.2-q21.1 reveals haploinsufficient genes influencing behavior and fat deposition.

[monosomy 21]

Haploinsufficiency of part of human chromosome 21 results in a rare condition known as Monosomy 21 . This disease displays a variety of clinical phenotypes , including intellectual disability , craniofacial dysmorphology , skeletal and cardiac abnormalities , and respiratory complications . To search for dosage-sensitive genes involved in this disorder , we used chromosome engineering to generate a mouse model carrying a deletion of the Lipi-Usp 25 interval , syntenic with 21 q 11 .2 -q 21 .1 in humans . Haploinsufficiency for the 6 genes in this interval resulted in no gross morphological defects and behavioral analysis performed using an open field test , a test of anxiety , and tests for social interaction were normal in monosomic mice . Monosomic mice did , however , display impaired memory retention compared to control animals . Moreover , when fed a high -fat diet (HFD ) monosomic mice exhibited a significant increase in fat mass /fat percentage estimate compared with controls , severe fatty changes in their livers , and thickened subcutaneous fat . Thus , genes within the Lipi-Usp 25 interval may participate in memory retention and in the regulation of fat deposition .

Diseases
Validation

Diseases presenting "severe fatty changes" symptom

monosomy 21

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