Examination of FGFRL1 as a candidate gene for diaphragmatic
defects at chromosome 4p16.3 shows that Fgfrl1 null mice have
reduced expression of Tpm3, sarcomere genes and Lrtm1 in the
diaphragm

J 2010

Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm

LOPEZJIMENEZ, Nelson; Simon GERBER; Vlad POPOVICI; Sonia MIRZA; Kirsten COPREN et al.

Základní údaje

Originální název

Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm

Autoři

LOPEZJIMENEZ, Nelson; Simon GERBER; Vlad POPOVICI; Sonia MIRZA; Kirsten COPREN; Linda TA; Gary M SHAW; Beat TRUEB a Anne M SLAVOTINEK

Vydání

Human Genetics, NEW YORK, SPRINGER, 2010, 0340-6717

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 5.047

Označené pro přenos do RIV

DOI

https://doi.org/10.1007/s00439-009-0777-8

UT WoS

000274456500006

Změněno: 4. 3. 2013 15:04, doc. Ing. Vlad Popovici, PhD

Anotace

V originále

Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this chromosome region can be deleted in patients with congenital diaphragmatic hernia (CDH). We examined FGFRL1 as a candidate gene for the diaphragmatic defects associated with 4p16.3 deletions and re-sequenced this gene in 54 patients with CDH. We confirmed six known coding single nucleotide polymorphisms (SNPs): c.209G > A (p.Pro20Pro), c.977G > A (p.Pro276Pro), c.1040T > C (p.Asp297Asp), c.1234C > A (p.Pro362Gln), c.1420G > T (p.Arg424Leu), and c.1540C > T (p.Pro464Leu), but we did not identify any gene mutations. We genotyped additional CDH patients for four of these six SNPs, including the three non-synonymous SNPs, to make a total of 200 chromosomes, and found that the allele frequency for the four SNPs, did not differ significantly between patients and normal controls (p a parts per thousand yen 0.05). We then used Affymetrix Genechip(A (R)) Mouse Gene 1.0 ST arrays and found eight genes with significantly reduced expression levels in the diaphragms of Fgfrl1 homozygous null mice when compared with wildtype mice-Tpm3, Fgfrl1 (p = 0.004), Myl2, Lrtm1, Myh4, Myl3, Myh7 and Hephl1. Lrtm1 is closely related to Slit3, a protein associated with herniation of the central tendon of the diaphragm in mice. The Slit proteins are known to regulate axon branching and cell migration, and inhibition of Slit3 reduces cell motility and decreases the expression of Rac and Cdc42, two genes that are essential for myoblast fusion. Further studies to determine if Lrtm1 has a similar function to Slit3 and if reduced Fgfrl1 expression can cause diaphragm hypoplasia through a mechanism involving decreased myoblast motility and/or myoblast fusion, seem indicated.

Citovat

LOPEZJIMENEZ, Nelson; Simon GERBER; Vlad POPOVICI; Sonia MIRZA; Kirsten COPREN; Linda TA; Gary M SHAW; Beat TRUEB a Anne M SLAVOTINEK. Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm. Human Genetics. NEW YORK: SPRINGER, 2010, roč. 127, č. 3, s. 325-336. ISSN 0340-6717. Dostupné z: https://doi.org/10.1007/s00439-009-0777-8.

@article{1090302,
   author = {LopezJimenez, Nelson and Gerber, Simon and Popovici, Vlad and Mirza, Sonia and Copren, Kirsten and Ta, Linda and Shaw, Gary M and Trueb, Beat and Slavotinek, Anne M},
   article_location = {NEW YORK},
   article_number = {3},
   doi = {https://doi.org/10.1007/s00439-009-0777-8},
   language = {eng},
   issn = {0340-6717},
   journal = {Human Genetics},
   title = {Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm},
   volume = {127},
   year = {2010}
}

TY  - JOUR
ID  - 1090302
AU  - LopezJimenez, Nelson - Gerber, Simon - Popovici, Vlad - Mirza, Sonia - Copren, Kirsten - Ta, Linda - Shaw, Gary M - Trueb, Beat - Slavotinek, Anne M
PY  - 2010
TI  - Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm
JF  - Human Genetics
VL  - 127
IS  - 3
SP  - 325-336
EP  - 325-336
PB  - SPRINGER
SN  - 03406717
N2  - Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this chromosome region can be deleted in patients with congenital diaphragmatic hernia (CDH). We examined FGFRL1 as a candidate gene for the diaphragmatic defects associated with 4p16.3 deletions and re-sequenced this gene in 54 patients with CDH. We confirmed six known coding single nucleotide polymorphisms (SNPs): c.209G > A (p.Pro20Pro), c.977G > A (p.Pro276Pro), c.1040T > C (p.Asp297Asp), c.1234C > A (p.Pro362Gln), c.1420G > T (p.Arg424Leu), and c.1540C > T (p.Pro464Leu), but we did not identify any gene mutations. We genotyped additional CDH patients for four of these six SNPs, including the three non-synonymous SNPs, to make a total of 200 chromosomes, and found that the allele frequency for the four SNPs, did not differ significantly between patients and normal controls (p a parts per thousand yen 0.05). We then used Affymetrix Genechip(A (R)) Mouse Gene 1.0 ST arrays and found eight genes with significantly reduced expression levels in the diaphragms of Fgfrl1 homozygous null mice when compared with wildtype mice-Tpm3, Fgfrl1 (p = 0.004), Myl2, Lrtm1, Myh4, Myl3, Myh7 and Hephl1. Lrtm1 is closely related to Slit3, a protein associated with herniation of the central tendon of the diaphragm in mice. The Slit proteins are known to regulate axon branching and cell migration, and inhibition of Slit3 reduces cell motility and decreases the expression of Rac and Cdc42, two genes that are essential for myoblast fusion. Further studies to determine if Lrtm1 has a similar function to Slit3 and if reduced Fgfrl1 expression can cause diaphragm hypoplasia through a mechanism involving decreased myoblast motility and/or myoblast fusion, seem indicated.
ER  -

LOPEZJIMENEZ, Nelson; Simon GERBER; Vlad POPOVICI; Sonia MIRZA; Kirsten COPREN; Linda TA; Gary M SHAW; Beat TRUEB a Anne M SLAVOTINEK. Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm. \textit{Human Genetics}. NEW YORK: SPRINGER, 2010, roč.~127, č.~3, s.~325-336. ISSN~0340-6717. Dostupné z: https://doi.org/10.1007/s00439-009-0777-8.

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