Investigator Finds Lost Mouse – 30 Years Later
JAX® NOTES Issue 510, Summer 2008
We all know how it feels to lose something – a favorite book, CD, tool, reference publication, data - and find it again. The thing may pop up in the most unusual and unexpected place and time, sometimes a week, a year, or, as was recently the case with Dr. Yash Kanwar of Northwestern University in Chicago, over 30 years later and half a continent away. Dr. Kanwar's lost item was a mouse, and he recently found it in one of our freezers. And now, here’s the rest of the story.
In the early and mid 1970’s Dr. Kanwar wrote his Ph.D. thesis and published several scientific journal articles on a mouse strain named PRO/Re. He obtained a pair of the mice, along with a few mice of the parental strains, C57BL/6J and 129/Re, from Dr. Elizabeth "Tibby" Russell of The Jackson Laboratory and produced a colony large enough to meet his research needs. Blake and Russell (1972) had already characterized the PRO/Re mouse as the only known mouse model of hyperprolinemia (high concentrations of proline in the plasma) and prolinuria (high concentrations of proline in the urine). In his thesis and other publications (Kanwar et al. 1975, 1977), Dr. Kanwar further described the morphological, biochemical, and pedigree characteristics of the mouse and established it as a unique model of chemically-induced renal disease, the characteristics of which are very similar to those of human nephrosis.
When Dr. Kanwar completed his studies, he sent the remaining mice to The Jackson Laboratory. Several times since, he has thought that he or someone else should resume research with the mouse. As he stated in an interview, "There are very few mice models of hyperprolinemia and proteinuria. The PRO/Re mouse is the only mouse model in which nephrosis can be induced chemically, as is traditionally done in the rat model, to study the pathogenesis of proteinuria. In the past decade, the extensive characterization of the mouse genome and phenome, along with the development of sophisticated technologies to produce genetically-engineered mice, make the PRO/Re mouse a superior model for discovering the genetic bases of hyperprolinemia and proteinuria in humans." However, up until a few months ago, Dr. Kanwar did not know if the PRO/Re mouse was still available. It was then that two of our field representatives, Laura Lockwood and Ray Tritch, met Dr. Kanwar in his laboratory at Northwestern University. Dr. Kanwar brought up the subject of the PRO/Re mouse as a model of human proteinuria and wondered if the mouse was still available from The Jackson Laboratory. The two representatives made a few phone calls to our Bar Harbor facility and learned that the mouse was indeed available – in one of our freezers. It had been cryopreserved as strain PRO/ReJ (000059) in 1981 and could be easily recovered.
After over 30 years, Dr. Kanwar was back in touch with his mouse.
Our records show that since the PRO/ReJ mouse was cryopreserved, it has been recovered for about a dozen customers. Due to time and funding constraints, Dr. Kanwar does not intend to resume his studies with the mouse, but he hopes that someone else will. By cross-breeding the PRO/ReJ strain with genetically-engineered strains that do not show any phenotype, researchers may discover the genetic bases of glomerular diseases such as proteinuria and Alport’s syndrome. And, we are excited about this unique story illustrating the value of cryopreserving little-used but potentially very valuable strains of mice for future researchers.
References
Blake RL, Russell ES. 1972. Hyperprolinemia and prolinuria in a new inbred strain of mice, PRO-Re. Science 176:809-11.
Jacquet H, Demily C, Houy E, Hecketsweiler B, Bou J, Raux G, Lerond J, Allio G, Haouzir S, Tillaux A, Bellegou C, Fouldrin G, Delamillieure P, Ménard JF, Dollfus S, D'Amato T, Petit M, Thibaut F, Frébourg T, Campion D. 2005. Hyperprolinemia is a risk factor for schizoaffective disorder. Mol Psychiatry 10:479-85.
Kanwar YS, Manaligod JR, Krakower CA. 1977. Aminonucleoside nephrosis in PRO/Re mice. Proc Soc Exp Biol Med 155:339-45.
Kanwar Y S, Krakower CA, Manaligod JR, Justice P, Wong PWK. 1975. Biochemical, morphological and hybrid studies in hyperprolinemic mice. Biomedicine 22:209-216.
In humans, hyperprolinemia is of two types. Type 1 hyperprolinemia is a rare inborn autosomal recessive disorder due to a deficiency in proline oxidase. Although the disease is generally believed to be benign, it has been reported to be associated with many abnormalities, including seizures, epilepsy, nerve deafness, mental retardation, and familial nephritis (Jacquet 2005; Kanwar 1975). Type 2 hyperprolinemia is characterized by a deficiency of delta-pyrroline-5-carboxylic acid. It is sometimes associated with convulsive disorders and mental retardation (Kanwar 1975).
