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 "anxiety" symptom

22q11.2 deletion syndrome

achondroplasia

adrenal incidentaloma

adrenomyeloneuropathy

cadasil

child syndrome

classical phenylketonuria

cohen syndrome

congenital adrenal hyperplasia

congenital toxoplasmosis

cutaneous mastocytosis

fabry disease

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

hereditary cerebral hemorrhage with amyloidosis

junctional epidermolysis bullosa

locked-in syndrome

monosomy 21

oligodontia

oral submucous fibrosis

phenylketonuria

von hippel-lindau disease

x-linked adrenoleukodystrophy

This symptom has already been validated