Strain information
 NBRP Rat No: 0904  Strain name: HHSE/Hat  Commmon Name: 弘前小眼球ヘアレスラット, HISER-HHR/Hat Rat Genome Database
Principal Investigator:  Takeshi Simizu  Hirosaki University       5 Zaifu-cho,    036-8562      Japan
Tel: 0172-39-5019    Fax: 0172-39-5020 Email: munchsan@hirosaki-u.ac.jp
Preservation Status:   Embryo        Sperm       Living Animals ../images/Photos/ ../images/Photos/
Coat Color  白色（乏毛のためやや褐色の様相）
Inbred Generations  F?+20
Usage Restrictions  In publishing the research results to be obtained by use of the BIOLOGICAL RESOURCE, a citation of the following literature(s) designated by the DEPOSITOR is requested.
Please select and cite articles related to your research contents from the following.
1.Hatayama etal.Establishment of Hirosaki Hairless Rat(HHR)strain.JPN J Clin Exp Med 1986; 139(3):215-216
2.Nanashima et al.Nuclear location of STAT5A modified with O-linked N-acetylglucosamine and early involution in the mammary gland of Hirosaki hairless rat.J Biol Chem.2005;280(52):43010-43016
3.Nanashima st al. The hairless phenotype of the Hirosaki hariless rat is due to the deletion of an 80-kb genomic DNA containing five basic keratin genes.J BiolChem.2008;283(24):16868-16875.
4.Yamada et al.Lectin-like receptor Ly49s3 on dendritic cells contributes to the deifferentiation of regulatory T cells in the rat thymus. J Immunol. 2013;191(7):3799-3809
5.Nanashima et al.Deletion of phospholipase A2 group IVc induces apoptosis in rat mammy tumour cells by the nuclear factor-kB/lipocalin 2 pathway. Biochen J. 2015;469(2):315-324.
6.Yamada et al. Establishment of a recessive mutant small-eye rat with lens involution and retinal detachment associated with partial deletion and rearrangement of the Cryba1 gene. Biochem J. 2015;471(2):293-305.
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Genetic Status
 Inbred  Segregating  Congenic  Consomic  Recombinant
 Coisogenic  Spont. Mutant  Transgene  Ind. Mutant  Category Other 
Comercial Availability
Research Category
 Diabetes Obesity  Neurobiology  Ophthalmology  Dentistry  Cardio Hypertension
 Cancer  Metabolism  Otorhinology  Immunology  Infectious
 Osteosis  Internal Organ  Dermatology  Reproduction  Development
 Behavior  Hematology  Urology  Pharmacology  Research Area Others 
 Control Strain  Marker Strain
Gene Affected ケラチン遺伝子（Kb21, Kb23, Kb25, Kb26, Krt2-25）、クリスタリン遺伝子（Cryba1）、ホスホリパーゼ遺伝子（Pla2g4c）およびレクチン様受容体遺伝子（Ly49s3）の欠失
Origin HHSE/Hat was derived from Hirosaki hairless rat (HHR) and Hirosaki small-eye rat (HiSER), which are Sprague-Dawley rat (SDR) mutant lines. HHR was established in 1984 as a spontaneous mutant of SDR that has been inbred in Department of Biochemistry and Genome Biology Hirosaki University Graduate School of Medicine. Whole body shows hypotrichosis, abnormal differentiation of thymus, and regressed mammary gland in females. These mutations are autosomal recessive and are suggested to be due to deletion of the keratin gene cluster and the lectin-like receptor gene Ly49s3. HiSER was established in 2013 as a spontaneous mutant of SDR maintained in our course in the same way as HHR. This mutation that retinal detachment is progressively exacerbated, is autosomal recessive and is suggested to be due to deletion of the crystallin gene Cryba1. The mutations in HHR and HiSER are on different chromosomes and do not affect each other.
Strain characteristics The whole body is scarce. Female rats cannot raise (suckle) a child due to the regressed mammary gland. Abnormal differentiation of the thymus is observed. Retinal detachment is progressively exacerbated. In addition, the eyeball size is small compared to normal one. These phenotypes are autosomal recessive inherited mutations.
Breeding Conditions Female rats of HHR homozygous mutant cannot suckle due to the regressed mammary gland. First, closs a male HHSE/Hat (F?+20) and a female SDR, and get pups. 1. Mate HHSE/Hat (F?+20) with female SDR. All of the offspring show normal-hair and normal-eye, and genotypes of HHR and HiSER are heterozygous. 2. Sib-mate by using the offspring (step 1). The phenotypes of offspring getting from this step are [normal-hair and normal-eye]:[hairless and small-eye]:[normal-hair and small-eye]:[hairless and small-eye (=HHSE/Hat)]=9:3:3:1. 3. Select the male rat showing [hairless and small-eye] from among the offspring getting from step 2 (observe the phenotypes). 4. Select a HHR heterozygous from among the female rats showing [normal-hair and small-eye] getting from step 2 by the genotyping (Described below). 5. Mate the male selected in step 3 with the female of selected step 4. The phenotypes of offspring are [normal-hair (hetero) and small-eye] or [hairless and small-eye]. 6. Select the male showing [hairless and small-eye] and the female showing [normal-hair and small-eye], and mate these rats. 7. Repeat step 5-6 for breeding.
Genotyping Decide heterozygous HHR mutant by genomic PCR. 1. Primer sequence F1: 5’-gctttgcttagtgccaggac-3’ R1: 5’-gggttgggaatgaatgacct-3’ F2: 5’-tagaacctgtcagcaactgatcc-3’ R2: 5’-gactggataagccccttgtg-3’ 2. PCR condition 1) Denature at 94℃ for 3 min 2) Denature at 94℃ for 30 sec 3) Annealing at 58℃ (F1 and R1) or 62℃ (F2 and R2) for 30 sec 4) Extension at 72℃ for 1 min 5) 2)-4) 35 cycles. 3. Selection 1) In the case of SDR and heterozygous, not homozygous, 213 bp DNA fragments are observed using by primer F1-R1. 2) In the case of heterozygous and homozygous, not SDR, 1171 bp DNA fragments are observed using by primer F2-R2. 3) If the DNA fragments in 1) and 2) are observed, the rat can be decided as heterozyogous. By the above methods, select the female of hoterozygous HHR mutants in "normal body hair and microphthalmia".
References 畑山一郎ら 弘前ヘアレスラット（HHR）の開発　医学のあゆみ　1986年　第139巻　第3号　215-216頁

Nanashima et al. Nuclear localization of STAT5A modified with O-linked N-acetylglucosamine and early involution in the mammary gland of Hirosaki hairless rat. J Biol Chem. 2005 Dec 30;280(52):43010-6.

Nanashima et al. The hairless phenotype of the Hirosaki hairless rat is due to the deletion of an 80-kb genomic DNA containing five basic keratin genes. J Biol Chem. 2008 Jun 13;283(24):16868-75.

Yamada et al. Lectin-like receptor Ly49s3 on dendritic cells contributes to the differentiation of regulatory T cells in the rat thymus. J Immunol. 2013 Oct 1;191(7):3799-3809 Nanashima et al. Deletion of phospholipase A2 group IVc induces apoptosis in rat mammary tumour cells by the nuclear factor-κB/lipocalin 2 pathway. Biochem J. 2015 Jul 15;469(2):315-24.

Yamada et al. Establishment of a recessive mutant small-eye rat with lens involution and retinal detachment associated with partial deletion and rearrangement of the Cryba1 gene. Biochem J. 2015 Oct 15;471(2):293-305.
Additional strain information