PMID- 10491259
OWN - NLM
STAT- MEDLINE
DCOM- 19991102
LR  - 20071115
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 214
IP  - 1
DP  - 1999 Oct 1
TI  - EMK protein kinase-null mice: dwarfism and hypofertility associated with
      alterations in the somatotrope and prolactin pathways.
PG  - 87-101
AB  - Gene trapping was used in embryonic stem (ES) cells in an attempt to inactivate
      genes involved in development. The Emk (ELKL motif kinase) gene has been
      disrupted and a mutant mouse line derived. Previous work had shown that EMK
      kinases, called MARK in the rat, exert a major control on microtubule stability
      by phosphorylating microtubule-associated proteins and that genes homologous to
      Emk in yeast or Caenorhabditis elegans are essential for cell and embryonic
      polarity. Although we found the Emk gene to be active in the preimplantation
      mouse embryo and then to show a widespread expression, Emk-null mice had no
      embryonic defect and were viable. They show an overall proportionate dwarfism and
      a peculiar hypofertility: homozygotes are not fertile when intercrossed, but are 
      fertile in other types of crosses. Insulin-like growth factor I (IGF I) and
      IGF-binding protein 3 (IGFBP3) were reduced in the plasma of homozygotes of both 
      sexes. A direct implication of the EMK kinase in IGF I plasmatic production is
      unlikely because the Emk gene does not seem to be expressed in hepatocytes.
      Nevertheless, GH assayed at arbitrary times in plasma did not show differences
      between genotypes and GH concentrations in pituitary extracts were not found to
      be altered in homozygotes. Our results, though, do not exclude the possibility
      that in the mutants the overall quantity of GH secreted daily is reduced. Our
      observation of a smaller size of the pituitaries of the mutants is in favor of
      this hypothesis. The prolactin concentration in the pituitaries was much lowered 
      in homozygous females, but it was normal in males. The possible involvement of
      EMK protein kinase in hormone secretion in the pituitary and/or the hypothalamus,
      via the microtubule network, is discussed.
CI  - Copyright 1999 Academic Press.
FAU - Bessone, S
AU  - Bessone S
AD  - Faculte des Sciences, Inserm U 470, Parc Valrose, Nice Cedex 2, 06108, France.
      bessone@unice.fr
FAU - Vidal, F
AU  - Vidal F
FAU - Le Bouc, Y
AU  - Le Bouc Y
FAU - Epelbaum, J
AU  - Epelbaum J
FAU - Bluet-Pajot, M T
AU  - Bluet-Pajot MT
FAU - Darmon, M
AU  - Darmon M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9002-62-4 (Prolactin)
RN  - 9002-72-6 (Growth Hormone)
RN  - EC 2.7.1.- (Mark2 protein, mouse)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Animals
MH  - Caenorhabditis elegans/embryology
MH  - *Cell Cycle Proteins
MH  - Crosses, Genetic
MH  - Dwarfism/*genetics
MH  - Embryonic and Fetal Development/*physiology
MH  - Female
MH  - Gene Expression Regulation, Developmental
MH  - Growth Hormone/blood/genetics
MH  - Heterozygote
MH  - Homozygote
MH  - Infertility/*genetics
MH  - Insulin-Like Growth Factor Binding Protein 3/blood/genetics
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Prolactin/*blood/genetics
MH  - Protein-Serine-Threonine Kinases/deficiency/*genetics/*metabolism
MH  - Rats
MH  - Restriction Mapping
MH  - Sex Characteristics
MH  - beta-Galactosidase/genetics
EDAT- 1999/09/24 00:00
MHDA- 1999/09/24 00:01
CRDT- 1999/09/24 00:00
PHST- 1999/09/24 00:00 [pubmed]
PHST- 1999/09/24 00:01 [medline]
PHST- 1999/09/24 00:00 [entrez]
AID - 10.1006/dbio.1999.9379 [doi]
AID - S0012-1606(99)99379-X [pii]
PST - ppublish
SO  - Dev Biol. 1999 Oct 1;214(1):87-101. doi: 10.1006/dbio.1999.9379.