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In utero Measurement of Heart Rate in Mouse by Noninvasive M-mode Echocardiography

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Congenital hydrocephalus in genetically engineered mice.

P Vogel¹, R W Read, G M Hansen

¹Lexicon Pharmaceuticals, Inc, 8800 Technology Forest Place, The Woodlands, TX 77381-1160, USA. pvogel@lexpharma.com

Veterinary Pathology

|July 13, 2011

Summary

Genetic factors contribute to congenital hydrocephalus. Studies using genetically engineered mice identified dysfunctional motile cilia as a cause in most cases, aiding understanding of this neurological disorder.

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Area of Science:

Genetics
Neurology
Developmental Biology

Background:

Genetic factors are implicated in the complex pathogenesis of hydrocephalus.
Identifying genes in animal models can reveal causes of cerebrospinal fluid accumulation in humans.

Purpose of the Study:

To identify genetic factors contributing to congenital hydrocephalus using genetically engineered mouse models.
To elucidate the role of dysfunctional motile cilia in hydrocephalus development.

Main Methods:

Utilized 12 lines of genetically engineered mice with autosomal recessive congenital hydrocephalus.
Analyzed knockout mouse models to identify genetic causes of the disorder.

Main Results:

Dysfunctional motile cilia were identified as the underlying cause in 8 of the 12 mouse lines.
Potential ciliary defects were suggested for the remaining 4 lines, with similarities to human ciliopathies.

Conclusions:

Genetically engineered mice are valuable for identifying genes involved in congenital hydrocephalus.
Findings suggest motile cilia dysfunction is a significant factor in hydrocephalus pathogenesis.
Mouse models can advance understanding of human hydrocephalus genetics and developmental pathways.