Dr. Cat Lutz

Cathleen Lutz, Ph.D.

Senior Research Scientist, GRS Repository Director

e: cat.lutz@jax.org p: 207-288-6341


My lab focuses on modeling human neurodegenerative disease in mice, with an emphasis on optimum use and best practices for research and preclinical drug testing. As part of the Mouse Model Repository at The Jackson Laboratory, my lab works with the NIH and multiple disease foundations to improve on existing mouse models, identify modifier genes, and generate new models that will facilitate therapeutic development. Our goal is to work with foundations, foundation partners and the scientific community to facilitate the rapid characterization, standardization and consistent use of mouse models, with the aim of accelerating treatment discovery. Presently we are focused on Spinal Muscular Atrophy (SMA), Friedreich's Ataxia, amyotrophic lateral sclerosis (ALS), and Rett syndrome.

Scientific report

Spinal Muscular Atrophy (SMA)
Spinal Muscular Atrophy (SMA) affects the motor neurons of the spinal cord and brain stem. These critically important cells are responsible for supplying electrical and chemical messages to muscle cells. Without the proper input from the motor neurons, muscle cells cannot function properly. The muscle cells will, therefore, become much smaller (atrophy) and will produce symptoms of muscle weakness.

Spinal Muscular Atrophy is caused by mutation in the gene SMN1 and kills more babies than any other genetic disease. Degeneration and death of the motor neurons (also called Anterior Horn Cells) in the brain stem and spinal cord produces weakness in limb muscles and in muscles used for swallowing and breathing. This disease afflicts infants, children and adults worldwide. It is estimated that spinal muscular atrophy occurs in between one-in-6,000 and one-in-20,000 births.

My lab has an ongoing relationship with the SMA Foundation to generate, characterize and distribute mouse models to the scientific community. Most recently, we have characterized a new model harboring an inducible Smn rescue allele and demonstrated that restoring SMN protein even after disease onset is sufficient to reverse neuromuscular pathology and effect robust rescue of the SMA phenotype. Importantly, our findings also indicate that there is a therapeutic window of opportunity, defined by the extent of neuromuscular synapse pathology and the ability of motor neurons to respond to SMN induction, following which restoration of the protein to the organism fails to produce therapeutic benefit. Nevertheless, our results suggest that even in severe SMA, timely re-instatement of the SMN protein may halt the progression of the disease and serve as an effective post-symptomatic treatment.

Friedreich's Ataxia
Friedreich's Ataxia is an inherited disease that causes progressive damage to the nervous system. Ataxia results from the degeneration of nerve tissue in the spinal cord and of nerves that control muscle movement in the arms and legs. Difficulty in walking usually begins between five and 15 years of age.

Generally, within 15 to 20 years after the appearance of the first symptoms, the person is confined to a wheelchair, and in later stages of the disease, individuals become completely incapacitated. Most people with Friedreich's ataxia die in early adulthood if there is significant heart disease, the most common cause of death. There is currently no effective cure or treatment for Friedreich's ataxia.

Our current efforts in Friedreich's Ataxia involve standardization of existing models onto a single uniform genetic background to compare and assess phenotypic onset and disease progression. Our molecular studies are designed to evaluate copy number stability in each model and assess mitochondrial dysfunction at various stages of development.

Amyotrophic lateral sclerosis (ALS)
Amyotrophic lateral sclerosis (ALS), often referred to as "Lou Gehrig's Disease," is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms.

Research in ALS mouse models has focused primarily on mutations in the SOD1 gene. The Mouse Model Repository at JAX has worked extensively over the years with numerous foundations and ALS researchers to provide stable and consistent models and have provided guidelines for preclinical testing and colony management to the scientific community.

Now, recent discoveries point to defects in RNA processing proteins as a key to understanding the causes of the disease and offering new hope for therapeutic intervention. Creation and rapid distribution of mouse models of these disorders is crucial to finding treatments for ALS. We have recently received funding from the ALS Association, the ALS Therapy Alliance as well as private philanthropic support to establish the National ALS Mouse Model Repository at The Jackson Laboratory. The goals of this endeavor are to standardize, characterize and distribute new mouse models in a consolidated effort to provide new tools to advance disease therapies and create cellular models using embryonic stem (ES) cells in the study of ALS.

Lab staff

Principal Investigator: Cathleen Lutz, Ph.D.
Senior Manager, Genetic Quality Control: Melissa Osborne, M.S.
Manager, GRS Genetic QC & QA: Greg Christianson, Ph.D.
Quality Control Technician: Laure Case, Ph.D.
GRS Product Manager: Karen Fancher, Ph.D. 
Colony Managers: Carrie Leduc, Phyllis Magnani, Keegan Wardwell
Research Associate: Laurent Bogdanik, Ph.D.
Research Assistant I:  Luis Cantor, Alison Kieffer
Project Manager: Crystal Davis, M.S. 
Manager Animal Care: Larry Wilson, M.S. 
Executive Assistant: Aimee Picard

Publication listings

Selected publications

Srivastava A, Philip VM, Greenstein I, Rowe LB, Barter M, Lutz C, Reinholdt LG. 2014. Discovery of transgene insertion sites by high throughput sequencing of mate pair libraries. BMC Genomics 15:356. PMCID: PMC4035081

Lutz CM, Osborne MA. 2014. Optimizing mouse models of neurodegenerative disorders: are therapeutics in sight? Future Neurol 9(1): 67-75. Review.

Hatzipetros T, Bogdanik LP, Tassinari VR, Kidd JD, Moreno AJ, Davis C, Osborne M, Austin A, Vieira FG, Lutz C, Perrin S. 2013. C57BL/6J congenic Prp-TDP43A315T mice develop progressive neurodegeneration in the myenteric plexus of the colon without exhibiting key features of ALS. Brain Res. Oct 18 2013  [Epub ahead of print]. PMID: 24141148

Taylor AS, Glascock JJ, Rose FF Jr, Lutz C, Lorson CL. 2013. Restoration of SMN to Emx-1 expressing cortical neurons is not sufficient to provide benefit to a severe mouse model of Spinal Muscular Atrophy. Transgenic Res. 2013 Mar 20 [Epub ahead of print]. PMCID: PMC3745810

Osborne M, Gomez D, Feng Z, McEwen C, Beltran J, Cirillo K, El-Khodor B, Lin MY, Li Y, Knowlton WM, McKemy DD, Bogdanik L, Butts-Dehm K, Martens K, Davis C, Doty R, Wardwell K, Ghavami A, Kobayashi D, Ko CP, Ramboz S, Lutz C. Characterization of behavioral and neuromuscular junction phenotypes in a novel allelic series of SMA mouse models. 2012. Hum Mol Genet. 21(20):4431-4447. PMCID: PMC3459466

Martinez TL, Kong L, Wang X, Osborne MA, Crowder ME, Van Meerbeke JP, Xu X, Davis C, Wooley J, Goldhamer DJ, Lutz CM, Rich MM, Sumner CJ. 2012. Survival Motor Neuron Protein in Motor Neurons Determines Synaptic Integrity in Spinal Muscular Atrophy. J Neurosci. 2012 Jun 20;32(25):8703-8715. PMCID: PMC3462658

Reinholdt LG, Ding Y, Gilbert GT, Czechanski A, Solzak JP, Roper RJ, Johnson MT, Donahue LR, Lutz C, Davisson MT. 2011. Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn. Mamm Genome 22(11-12):685-691. PMCID: PMC3505986

Lutz C, Kariya S, Patruni S, Osborne MA, Liu DP, Henderson CE, Li DK, Pellizzoni L, Rojas J, Valenzuela DM, Murphy AJ, Winberg ML, Monani UR. 2011. Post-symptomatic restoration of SMN rescues the disease phenotype in severe spinal muscular atrophy (SMA) model mice. Journal of Clinical Investigation 121(8): 3029-41.  PMCID: PMC3148744

Gogliotti RG, Lutz C, Jorgensen M, Huebsch K, Koh S, Didonato CJ. 2011. Characterization of a commonly used mouse model of SMA reveals increased seizure susceptibility and heightened fear response in FVB/N mice. Neurobiol Dis. 2011 Jul;43(1):142-51. PMCID: PMC3679180

Heier CR, Satta R, Lutz C, DiDonato CJ. 2010. Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice. Hum Mol Genet 19(20):3906-18. PMCID: PMC2947406

Gogliotti RG, Hammond SM, Lutz C, Didonato CJ. 2010. Molecular and phenotypic reassessment of an infrequently used mouse model for spinal muscular atrophy. Biochem Biophys Res Commun 39(1):517-22. PMCID: PMC2814331

Workman E, Saieva L, Carrel TL, Crawford TO, Liu D, Lutz C, Beattie CE, Pellizzoni L, Burghes AH. 2009. A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice. Hum Mol Genet 18(12):2215-29. PMCID: 2685758

Sumner CJ, Wee CD, Warsing LC, Choe DW, Ng AS, Lutz C, Wagner KR. 2009. Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice. Hum Mol Genet 18(17):3145-52. PMCID: PMC2733819

Miki T, Zwingman TA, Wakamori M, Lutz CM, Cook SA, Hosford DA, Herrup K, Fletcher CF, Mori Y, Frankel WN, Letts VA. 2008. Two novel alleles of tottering with distinct Ca(v)2.1 calcium channel neuropathologies. Neuroscience 155(1):31-44. PMCID: PMC2633778

Kariya S, Park GH, Maeno-Hikichi Y, Leykekham O, Lutz CM, Arkovitz MS, Landmesser LT, Monani UR. 2008. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet 17(16):2552-2569. PMCID: PMC2722888

Book Chapters
Festing M, Lutz CM. Laboratory Animal Genetics and Genetic Quality Control. 3rd edition, In:  Handbook of Laboratory Animal Science.  Jann Hau, and Steven J. Schapiro (eds.), Taylor and Francis Group,  Volume 1, Chapter 9.   

Festing M, Lutz CM. Introduction to laboratory animal genetics. 8th edition, In: The Care and Management of Laboratory and Other Research Animals. Hubrecht R, Kirkwood J (eds.), Wiley-Blackwell, UK, Part 1, Chapter 4. 2010.

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