JARID2

Jarid2 (jumonji, AT rich interactive domain 2) is a protein coding gene that functions as a putative transcription factor. Distinguished as a nuclear protein necessary for mouse embryogenesis, Jarid2 is a member of the jumonji family that contains a DNA binding domain known as the AT-rich interaction domain (ARID)[2, 8, 11, 13]. In vitro studies of Jarid2 reveal that ARID along with other functional domains are involved in DNA binding, nuclear localization, transcriptional repression [5], and recruitment of Polycomb-repressive complex 2 (PRC2) [9, 10]. Intracellular mechanisms underlying these interactions remain largely unknown.

In search of developmentally important genes, Jarid2 has previously been identified by gene trap technology as an important factor necessary for organ development [2, 3, 5]. During mouse organogenesis, Jarid2 is involved in the formation of the neural tube and development of the liver, spleen, thymus and cardiovascular system [6, 12]. Continuous Jarid2 expression in the tissues of the heart, highlight its presiding role in the development of both the embryonic and the adult heart [2]. Mutant models of Jarid2 embryos show severe heart malformations, ventricular septal defects, noncompaction of the ventricular wall, and dialated atria [4]. Homozygous mutants of Jarid2 are found to die soon after birth [4]. Overexpression of the mouse Jarid2 gene has been reported to repress cardiomyocyte proliferation through it close interaction with retinoblastoma protein (Rb), a master cell cycle regulator [3, 5, 7]. Retinoblastoma-binding protein-2 and the human SMCX protein share regions of homology between mice and humans [1, 14].

Model organisms

Jarid2 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of JARID2 function. A conditional knockout mouse line, called Jarid2^{tm1a(KOMP)Wtsi} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out and two phenotypes were reported. Homozygous mutant embryos were identified during gestation but almost half showed signs of oedema, and in a separate study, only 1% survived until weaning (significantly less than the Mendelian ratio). The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.

External links

• JARID2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.