We previously reported
Israa
(
immune-system-released activating agent
), a novel gene nested in intron 6 of the mouse
Zmiz1
gene.
Zmiz1
is involved in several functions such as fertility and T cell development and its knockout leads to non-viable embryos. We also reported ISRAA's expression in lymphoid organs, particularly in the thymus CD
3+
T cells during all developmental stages. In addition, we showed that ISRAA is a binding partner of Fyn and Elf-1 and regulates the expression of T cell activation-related genes
in vitro
. In this paper, we report the generation and characterization of an
Israa
−/−
constitutive knockout mouse. The histological study shows that
Israa
−/−
mice exhibit thymus and spleen hyperplasia.
Israa
−/−
derived T cells showed increased proliferation compared to the wild-type mice T cells. Moreover, gene expression analysis revealed a set of differentially expressed genes in the knockout and wild-type animals during thymus development (mostly genes of T cell activation pathways). Immunological phenotyping of the thymocytes and splenocytes of
Israa
−/-
showed no difference with those of the wild-type. Moreover, we observed that knocking out the
Zmiz1
intron embedded
Israa
gene does not affect mice fertility, thus does not disturb this
Zmiz1
function. The characterization of the
Israa
−/-
mouse confirms the role ISRAA plays in the expression regulation of genes involved in T cell activation established
in vitro
. Taken together, our findings point toward a potential functional interrelation between the intron nested
Israa
gene and the
Zmiz1
host gene in regulating T cell activation. This constitutively
Israa
−/−
mice can be a good model to study T cell activation and to investigate the relationship between host and intron-nested genes.
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