SARCOSPAN-DEFICIENT MOUSE AS A MODEL FOR CLINICAL DISORDERS ASSOCIATED WITH SARCOSPAN MUTATIONS

摘要

Disclosed is a mouse, and cells derived therefrom, homozygous for a disrupted sarcospan gene, wherein the disruption in the gene is introduced into the mouse or an ancestor of the mouse at an embryonic stage, wherein the disruption prevents the synthesis of functional sarcospan in cells of the mouse. The mouse is characterized as weighing substantially more, and having substantially larger deposits of white adipose tissue, as compared to an otherwise genetically identical mouse lacking a disrupted sarcospan gene. Methods for production of the mouse are presented. Also disclosed is a method for diagnosing an individual with a clinical disorder associated with reduced expression of sarcospan. The method comprises providing a tissue biopsy sample from the individual and then quantitatively detecting sarcospan expression in cells of the sample. Sarcospan expression is also quantitatively detected in a comparable control sample obtained from a control individual known to exhibit normal expression of sarcospan, by otherwise identical means, and the two determined amounts are compared. Preferred cells for biopsy and techniques for determination of sarcospan expression are presented. Also disclosed is a method for diagnosing an individual with a clinical disorder associated with a mutation in the sarcospan gene. The method comprises isolating nucleic acids encoding the sarcospan gene, or a portion thereof, from the individual and then analyzing the nucleic acids by means to identify a mutation predicted to alter sarcospan expression or function in comparison to wild-type, with identification of the mutation being indicative of the presence of the clinical disorder in the individual. Suitable means for identifying a sarcospan mutation include PCR amplification and sequencing. Methods for treating an individual diagnosed with a clinical disorder associated with a mutation in the sarcospan gene by gene replacement therapy are also presented. Also disclosed is a method for identifying a therapeutic agent for the treatment of an individual diagnosed with a clinical disorder associated with a sarcospan mutation, and also a method for identifying an agent which reduces weight gain in an individual. The identification of a specific polymorphism in the sarcospan gene for use in linkage studies is also disclosed, as is a rapid method for determination of the presence of the polymorphism in an individual.