The N/NIH HS is the only rat HS population that we are aware of; it was first established at the National Institute of Health (NIH) in 1984 [46] and was derived from the following eight inbred progenitor (founder) strains: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N, and WN/N. The HS rat colony was maintained using a rotational breeding strategy and 60 breeder pairs by Dr. Carl Hansen at NIH until 2003. From 2003 to 2006, the colony was transferred to the laboratory of Dr. Eva Redei at Northwestern University and the number of breeder pairs decreased to 25. In 2006, the HS colony was transferred to two locations: Dr. Solberg Woods at the Medical College of Wisconsin and Dr. Alberto Fernando Teruel at the Autonomous University of Barcelona in Spain. At that time, the colony had been through 55 generations of breeding (50 at the NIH and 5 at Northwestern University). At MCW the number of breeding pairs was increased to 46 and the colony was maintained using a rotational breeding strategy [1, 23]. The HS animals at the Medical College of Wisconsin were named NMcwi:HS (Rat Genome Database identification number: 2314009). In 2013, after 15 generations of breeding at MCW (70 total), the colony was expanded to include 64 breeder pairs per generation and have been maintained in this way since that time. At that time a new breeding strategy that uses kinship coefficients was employed (https://github.com/pcarbo/breedail). As of early 2018, the colony had been through 81 generations of breeding. This HS rat colony is currently a national resource funded through a NIDA Center of Excellence for genome-wide association studies (GWAS) in outbred rats (P50DA037844) which seeks to identify genetic loci underlying drug abuse behaviors (seewww.ratgenes.org). Dr. Solberg Woods’ laboratory currently ships rats to several investigators throughout the United States, on a cost-recovery basis (enquiries to: lsolberg@wakehealth.edu). As of this writing, the HS colony is being maintained at both the Medical College of Wisconsin (MCW) and Wake Forest School of Medicine (WFSM); however, the MCW colony will be phased out by the end of 2019.
HS rats have also been used for GWAS. They were first used to fine-map a previously identified locus for glucose tolerance [47, 48], which led to identification of Tpcn2 as the likely underlying causal gene [49]. They were subsequently used to map multiple behavioral and physiological traits [50]. Since then they have been used for genetic mapping of adiposity [6] and studies show that the HS rat will be a promising model for mapping kidney-related traits [51], bone fragility [52], drug abuse behavior [53-55], depression-like behavior [10], as well as behavioral and physiological responses to stress [56-58] and ethanol [59-61].