RTL1 gene a likely culprit behind temple and Kagami-Ogata syndromes


Date:
October 6, 2020
Source:
Tokyo Medical and Dental University
Summary:
Researchers have found that Rtl1, which is a mouse ortholog of
the human RTL1 gene, appears to be the major gene responsible for
muscle and placental defects in models of Temple and Kagami-Ogata
syndromes, which are serious genetic conditions. Theirs is the first
study to demonstrate that a domesticated gene that is specific to
placental mammals plays an important role in fetal and neonatal
muscle development.



FULL STORY ========================================================================== Temple and Kagami-Ogata syndromes are serious genetic conditions that
can lead to a variety of health problems with neonatal lethality, and
in the case of Temple syndrome, severe growth problems occur. However,
the genetic mechanisms of these illnesses are not well understood. But
now, researchers from Tokyo Medical and Dental University (TMDU) have identified a gene that appears to be responsible for symptoms of both conditions, with important implications for human evolutionary genetics.


==========================================================================
In a study published last month in Development the research team has
revealed that deficiency and overproduction of Retrotransposon Gag
like 1 (Rtl1), which is a mouse ortholog of the human RTL1 gene, is significantly associated with muscle symptoms in models of Temple and Kagami-Ogata syndromes, respectively.

Temple and Kagami-Ogata syndromes are characterized by unique postnatal
muscle- related symptoms and prenatal placental problems. Although
Rtl1 has previously been found to be responsible for prenatal placental malformations in mouse models of these conditions, the causative gene
for the muscle-related symptoms has not been identified. The researchers
at Tokyo Medical and Dental University (TMDU) aimed to address this in
their recent study.

"Although Rtl1 is essential for maintaining placental fetal capillaries,"
says lead author of the study, Moe Kitazawa, "Little is known about the
role of Rtl1 in other forms of muscular abnormalities." The researchers extensively examined the role of Rtl1 in fetal muscle development at
both the cellular and tissue level. They used two previously generated
mouse models, one with a loss of Rtl1 to model Temple syndrome, and one
with an overproduction of Rtl1 to model Kagami-Ogata syndrome.

"Our data clearly demonstrate that RTL1 is of critical physiological significance," explains Fumitoshi Ishino, senior author. "In the mouse
models of both Temple and Kagami-Ogata syndrome, we detected severe
but distinct abnormalities in the neonatal muscles that are necessary
for respiration, such as the intercostal, abdominal, and diaphragm
muscles." Particularly, the overproduction of Rtl1 in the mouse model
of Kagami-Ogata syndrome led to respiratory problems and muscle damage, resulting in neonatal death and the loss of Rtl1 was a major cause of
abnormal muscle tone, such as hypotonia, and likely to be associated
with feeding difficulty/poor sucking function in Temple syndrome patients.

Thus, RTL1 appears to be the major gene responsible for muscle and
placental defects in these two genetic conditions.

"This is the first demonstration that a form of RTL1 specific to
eutherians (placental mammals) plays an important role in fetal and
neonatal muscle development," says Kitazawa.

"This work demonstrates that LTR retrotransposons, which are a specific
type of mobile DNA from which RTL1 originated, have influenced a variety
of eutherian- specific traits, including the skeletal muscles, placenta,
and the brain. Thus, these findings have important implications for understanding the acquisition of genes throughout the process of eutherian evolution," say senior authors Kaneko-Ishino and Ishino.


========================================================================== Story Source: Materials provided by
Tokyo_Medical_and_Dental_University. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Moe Kitazawa, Shinichiro Hayashi, Michihiro Imamura, Shin'ichi
Takeda,
Yumiko Oishi, Tomoko Kaneko-Ishino, Fumitoshi Ishino. Deficiency
and overexpression of Rtl1 in the mouse cause distinct
muscle abnormalities related to Temple and Kagami-Ogata
syndromes. Development, 2020; 147 (21): dev185918 DOI:
10.1242/dev.185918 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201006114241.htm

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