An explanation of unexpected Hoxd expressions in mutant mice

نویسنده

  • Spyros Papageorgiou
چکیده

The Hox gene collinearity enigma has often been approached using models based on biomolecular mechanisms. The 'biophysical model', is an alternative approach, speculating that collinearity is caused by physical forces pulling the Hox clusters from a territory where they are inactive to a distinct spatial domain where they are activated in a step by step manner. Hox gene translocations have recently been observed in support of the biophysical model. Furthermore, genetic engineering experiments, performed in embryonic mice, gave rise to some unexpected mutant expressions that biomolecular models could not predict. In several cases when anterior Hoxd genes are deleted, the expression of the genes whose expression is probed in the mutants are 'impossible to anticipate'. On the contrary, the biophysical model offers convincing explanation. All these experimental results support the idea of physical forces being responsible for Hox gene collinearity. In order to test the validity of the various models further, certain experiment involving gene deletions are proposed. The biophysical and biomolecular models predict different results for these experiments, hence the expected outcome will confirm or question the validity of these models.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Point Mutation of Hoxd12 in Mice

PURPOSE Genes of the HoxD cluster play a major role in vertebrate limb development, and changes that modify the Hoxd12 locus affect other genes also, suggesting that HoxD function is coordinated by a control mechanism involving multiple genes during limb morphogenesis. In this study, mutant phenotypes were produced by treatment of mice with a chemical mutagen, N-ethyl-N-nitrosourea (ENU). We an...

متن کامل

Male accessory sex organ morphogenesis is altered by loss of function of Hoxd-13.

The role of the Hox gene Hoxd-13 in postnatal morphogenesis of the male accessory sex organs was examined by correlating the distribution and temporal regulation of expression in the accessory sex organs of postnatal mice with morphologic abnormalities of Hoxd-13-deficient transgenic mice. Previous studies of Hoxd-13 expression in the perinatal period have shown a broad domain of expression in ...

متن کامل

A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse.

Using gene targeting in mice, we have undertaken a systematic mutational analysis of the homeobox-containing 5' HoxD genes. In particular, we have characterized the limb defects observed in mice with independent targeted disruptions of hoxd-12 and hoxd-13. Animals defective for hoxd-12 are viable, fertile, and appear outwardly normal yet have minor autopodal defects in the forelimb which includ...

متن کامل

Mutant Profilin1 Aggregation in Amyotrophic Lateral Sclerosis: An in Vivo Biochemical Analysis

Introduction: Profilin1 (PFN1) is a ubiquitously expressed protein known for its function as a regulator of actin polymerization and dynamics. A recent discovery linked mutant PFN1 to Amyotrophic Lateral Sclerosis (ALS), which is a fatal and progressive motor neuron disease. We have also demonstrated that Gly118Val mutation in PFN1 is a cause of ALS, and the formation of aggregates containing m...

متن کامل

Targeted disruption of Hoxd-10 affects mouse hindlimb development.

Targeted disruption of the Hoxd-10 gene, a 5' member of the mouse HoxD linkage group, produces mice with hindlimb-specific defects in gait and adduction. To determine the underlying causes of this locomotor defect, mutant mice were examined for skeletal, muscular and neural abnormalities. Mutant mice exhibit alterations in the vertebral column and in the bones of the hindlimb. Sacral vertebrae ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2012