FAQ Research Models GB

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1. What is the strain nomenclature?

Outbred stock

1) Laboratory Code holding the stock -> 2) Laboratory Code holding the original stock -> 3) The two points : -> 4) Strain symbol.

Outbred stocks are genetically undefined; that is, no two individuals from an outbred stock are the same. The purpose of an outbred stock is to maintain maximum heterozygosity.

Exemple: SPRAGUE DAWLEY RjHan: SD = Rj for Janvier Labs (Centre d’élevage Roger Janvier) + Han for Hannover + the two points + SD for Sprague Dawley.

 

Inbred stock

1) Strain symbol -> 2) Slash, / -> 3) Laboratory Code holding the original stock -> 4) Laboratory Code holding the stock.

An inbred strain should be designated by a unique brief symbol made up of uppercase, Roman, letters, or a combination of letters and numbers beginning with a letter. (Note that some pre-existing strains do not follow this convention; e.g., mouse strain 129P1/J). Inbred strains that have a common origin, but are separated before F20 are related inbred strains and symbols should reflect this relationship. Substrains are given the root symbol of the original strain, followed by a forward slash and a substrain designation.

Exemple: BROWN NORWAY BN/OrlRj = BN for Brown Norway + slash + Orl for Orléans CSAL + Rj for Janvier Labs (Centre d’élevage Roger Janvier).

 

Mutant stock

Inbred mutant stock:

1) Strain symbol -> 2) Laboratory Code holding the original stock -> 3) Laboratory Code holding the stock -> 4) gene + mutation. 

Exemple: Balb/cAnNRj–Foxn1nu/nu = Balb/cAn for the strain + N for NIH + Rj for JANVIER LABS (Centre d’élevage Roger Janvier) + Foxn1 for the gene + nu/nu for the mutation on the gene.

Except for the obese and diabetic mice nomenclature: 1) Strain symbol -> 2) gene + mutation -> 3) slash -> 4) Laboratory Code holding the original stock -> 5) Laboratory Code holding the stock (Obese B6.V-Lepob/JRj; Diabetic BKS(D)-Leprdb/JOrlRj)

Outbred mutant stock:

1) Laboratory Code holding the stock -> 2) Strain symbol -> 3) gene + mutation. 

Exemple: RjNMRI–Foxn1nu/nu = Rj for JANVIER LABS (Centre d’élevage Roger Janvier) + NMRI for the strain + Foxn1 for the gene + nu/nu for the mutation on the gene.

 

Hybrid stock

1) abbreviated strain symbol for females -> 2) abbreviated strain symbol for male -> 3) F1 à 4) slash, / -> 5) Laboratory Code holding the original stock -> 6) Laboratory Code holding the stock.

Exemple: B6CBAF1/JRj = B6 for female C57BL/6J + CBA for male CBA/J + F1 for the first generation of the cross + slash + J for The Jackson Laboratory + Rj for JANVIER LABS (Centre d’élevage Roger Janvier).

Other abbreviated strain symbol: D2 for DBA/2J, SJL for SJL/J, C for BALB/cJ, C3 for C3H

 

 

2. Laboratory Registration code or Laboratory code

Laboratory Registration Code or Laboratory code identifies a particular institute, laboratory, or investigator that produced, and may hold stocks of, for example, a DNA marker, a mouse or rat strain, or were the creator of a new mutation. Laboratory codes can be assigned through MGD (or MGI), RGD or directly by the ILAR.

  • RjJANVIER LABS(Centre d’élevage Roger Janvier)
  • JThe Jackson Laboratory
  • NNational Institute of Health (NIH)
  • HanHannover – Zentralinstitut fur Versuchstierzucht
  • HeW. E. Heston
  • OrlOrléans CSAL – Institut de transgenose TAAM UPS44
  • IbmmInstitut de Biologie et de Médecine Moléculaire (Universite libre de Bruxelles)
  • IcrInstitute for Cancer Research
  • TubTumblebrook Farm (Tum)
  • AlhnAgnes Lehuen (INSERM U25, hospital Necker)
  • LpfFrançoise Lepault (INSERM U561, hôpital St Vincent de Paul)
  • PasInstitut Pasteur
  • KyoKyoto University

 

Accede to Institute for Laboratory Animal Research #1 ILAR or #2 ILAR 

Accede to Mouse Genome Informatics (MGI) 

Accede to Rat Genome Database (RGD)

 

3. How to define the qualities of a breeder?

Excellent breeder: 

  • very productive
  • large litters (> 10)
  • very good parent (adoption, maternal,…)

 

Good breeder:

  • productive
  • medium litters (6 - 10)
  • good parent

 

Challenging breeder:

  • not productive
  • little litters (6-10)
  • bad parental qualities (cannibalism, lactation defects, …)

 

4. What is the vision in albino animals?

In albino animals, the retinal pigment epithelium is depigmented due to the lack of melanin that shows a red iris. Albino individuals, regardless of species, have impaired vision. The literature describes in particular the effects of albinism in rats.

Thus, albino animals have a decreased visual acuity. The inability of these animals to control the levels of the incoming light and the scattering of light inside the eye leads to progressive retinal degeneration. Experiences (Prusky et al. 2000; Prusky et al. 2002) showed that the pigmented rat had visual acuity of 20/600 (1 cpd) and an albino rat of 20/1200 vision (0.5 cpd).

Albino animals have impaired vision due to full / low light. Indeed, in pigmented animals, the iris controls the arrival of light on the retina. In albinos, this lack of pigment that light passes through the iris and the retina is dazzled. In bright light, albinos do not see.

The rods need a precursor of melanin to develop (DOPA), which can not be the case in albino, about 30% of the rods do not grow (Ilia et al. 2000). In addition, they are deficient in rhodopsin photoreceptor pigment (Grant et al. 2001). The rods are useful for detecting low levels of light, albino rats may therefore be difficult to see in low light conditions.

Albino rats need more time to adapt to the dark (3 h) of pigmented rats (30 min) (Behn et al. 2003). The lack of melanin in the eyes reduces the bioavailability of calcium (Drager, 1985) which plays a key role in the ability of the retina to adapt to low light conditions (Fain et al. 2001).

Albino individuals have difficulty with coordination. In normal mammals, the left side of each eye is connected to the right hemisphere of the brain and vice versa. In albinos, the majority of the left eye is connected to the right hemisphere and vice versa (Silver and Sapiro, 1981). In addition, projections of neurons involved in vision are disorganized (Creel et al. 1990). As a result, albinos may have difficulty coordinating and image processing.

In albino individuals, the perception of depth and movement changes. Albino rats, poor eyesight led to a poor perception of visual depth (Schiffmann et al. 1970). Albino rats have impaired vision of movement compared to pigmented rats (Hupfeld and Hoffman, 2006) vision.

In albino individuals, optical fibers are altered. For example, albino rats have abnormal fibers compared to pigmented rats; fibers in pigmented rats show more numerous "ball joints" than in albino rats. In albinos, optical fiber membranes are often broken (Yamada et al. 2002).

 

5. How was the change from Ly5 to CD45 to Ptprc gene?

Protein tyrosine phosphatase receptor type c also known as PTPRC is an enzyme that is encoded by the ptprc gene (chromosome 1). Ptprc encodes CD45, a protein tyrosine phosphatase which is expressed in nucleated hematopoietic cells and is required for their activation. PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leukocyte common antigen.

CD45 is signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. It has been shown to be an essential regulator of T- and B-cell antigen receptor (TCR and BCR) signaling and T cell development. It is expressed in lymphomas, B-cell chronic lymphocytic leukemia, hairy cell leukemia, and acute nonlymphocytic leukemia.

History 

Komura et al. (1975) first described a T cell antigen and classified it as Ly5.1 in C57BL/6 mice and Ly5.2 in SJL mice. To follow gene nomenclature, these designations became Ly5a for the B6 and Ly5b for the SJL.

In 1987, Morse et al. proposed a change in murine lymphocyte antigen names, which led to a reversal of the previous designation. Thus, beginning in 1987, the B6 genotype became Ly5b (Ly5.2 antigen specificity) and the SJL became Ly5a (Ly5.1).

An additional change was made in 1992, when the gene name changed to Cd45, leading to SJL designation as Cd45a (Cd45.1) and B6 designation as Cd45b (Cd45.2).

Finally, the gene name was changed to Ptprc in 1993, after work by Charbonneau et al. demonstrated homology between a tyrosine phosphatase and CD45 protein. This led to the current designations of the B6 as Ptprcb and the SJL as Ptprca.

In addition to the SJL, the Ptprca (Ly5.1) allele is also carried by the STS/A and DA strains. The Ptprcb (Ly5.2) allele is expressed by the C3H, DBA/2, and AKR strains as well as the C57BL/6. 

 

 

Strain

 

Designation

Chronology

1975

1987

1992

1993

 

SJL

Gene

Ly5b

Ly5a

Cd45a

Ptprca

Ag Specificity

Ly5.2

Ly5.1

Cd45.1

 

 

C57BL/6

Gene

Ly5a

Ly5b

Cd45b

Ptprcb

Ag Specificity

Ly5.1

Ly5.2

Cd45.2

 

 

Mutation

The recessive a or b mutation (chromosome 1) is a nucleotide substitution: sequencing of Ptprc identified a T to C point mutation resulting in a phenylalanine to serine missense mutation.  Twelve nucleotide differences between the a and b alleles have been identified. These base substitutions correspond to five amino-acid changes within the extracellular domain of the encoded protein. These amino-acid differences are clustered in a region that also contains the greatest divergence between mouse and rat sequences.

Homozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

These mice contain only 15% of the normal level of CD45 expression on the surface of nucleated hematopoietic cells, without altering splicing of transcript isoforms. These mutant mice may be useful in studying the differential regulation of TCR signaling by altered CD45 expression levels.

Homozygous null mutants have defective T cell, B cell, and NK cell morphology and physiology. Mice carrying an engineered point mutation exhibit lymphoproliferation and autoimmunity that leads to premature death.

References

  • Fischer et al.1991, Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes, Science 253: 401-406.
  • Charbonneau et al. 1988, The leukocyte common antigen (CD45): a putative receptor-linked protein tyrosine phosphatase, PNAS USA 85(19):7182-6.
  • Morse et al. 1987, Genetic nomenclature for loci controlling mouse lymphocyte antigens, Immunogenetics 25(2):71-8.
  • Komura et al. 1975, Ly-5: a new lymphocyte antigen system, Immunogenetics 1:452-6.
  • The Jackson Laboratory (JAX® NOTES Issue 458, Summer 1994)

 

6. What is Apolecia (loss of hair) in C57BL/6J and Related strains?

Alopecia is a characteristic of the C57BL/6J strain.

The origin of this phenomenon remains uncertain:

  • This was attributed to behavioral phenomena such overgrooming / barbering. Hair loss due to overgrooming (hair nibbling, whisker-eating) has been observed. In every case where overgrooming occurs the hair will grow back again if the mice are separated into individually occupied cages. If only one whisker-eating mouse is present in a cage, it can be readily identified by its own full set of whiskers
  • Initially, this phenomenon has been associated with behavior "dominance" or of "aggression"
  • Currently, the assumption changes and the track would move to an abnormal repetitive behavior (similar to OCD in humans)
  • Genetic predisposition and environmental factors are involved.

 

Alopecia begins shortly after weaning; it is growing around the age of 8-9 weeks and can reach a vast majority of animals of this age. The occurrence of hair loss, the size and shape of the affected area and the frequency of a particular pattern are variable. Mice of the C57BL substrains are much more prone to hair loss than other strains and certain congenic histocompatibility strains are especially susceptible. There may also be an individual variation.

Most often alopecia begins dorsally, with various degrees of damage. Some cases may progress to acute ulcer which can heal with a bed of granulation tissue, a pseudo-épithéliomateuse hyperplasia and scarring. Others have varying degrees of itching that can lead to progressive ulcerative disease requiring euthanasia.

Thus, alopecia includes a slight focal alopecia, chronic ulcerative dermatitis and scarring alopecia which can be separated into:

  • "Barbering" / trichotillomania for mild alopecia affecting areas of the head
  • Focal alopecia present on the body that often begins on the dorsal skin behind the ears and may progress to chronic ulcerative dermatitis.

 

The body alopecia and ulcerative dermatitis are poorly understood. The data showed a predilection of this disease in females. The severity and frequency are based on nutritional factors and rearing conditions (type of food, weaning age, humidity).

Hair loss caused by overgrooming is not a problem in our colonies. We are aware of the situation, the cause in not clearly understood, and the method of prevention (other than isolating the mice) is not known.

An alternative could be working on the C57BL/6N less sensitive to this phenomenon of alopecia (Cf. “Differences between C57BL/6J and C57BL/6N”).

References

  • Sundberg et al. 2011, Primary follicular dystrophy with scarring dermatitis in C57BL/6 mouse substrains resembles central centrifugal cicatricial alopecia in humans, Vet Pathol. 48(2):513-24.
  • Kalueff et al. 2006, Hair barbering in mice: implications for neurobehavioural research, Behav Processes. 71(1):8-15.
  • Garner et al. 2004, Barbering (fur and whisker trimming) by laboratory mice as a model of human trichotillomania and obsessive-compulsive spectrum disorders, Comp Med. 54:216-24.
  • Sarna et al. 2000, The Dalila effect: C57BL6 mice barber whiskers by plucking, Behav Brain Res. 108:39-45.
  • JAX® NOTES, 1987, Alopecia (loss of hair) in C57BL/6J and Related Strains, JAX® NOTES. 431.
  • Militzer and Wecker, 1986, Behavior associated alopecia areata in mice, Laboratory Animals 20:9-13.
  • Strozik and Festing, 1981, Whisker trimming in mice, Laboratory Animals 15:309-312.
  • Litterst, 1974, Mechanically self-induced muzzle alopecia in mice, Lab Animal Science 24:806-809.
  • Thornburg et al. 1973. The pathogenesis of the alopecia due to hair chewing in mice, Lab. Animal Sciences 23:843-850.
  • Long, 1972, Hair-nibbling and whisker-trimming as indicators of social hierarchy in mice, Animal Behavior 20:10-12.
  • Clark and Schein, 1966, Activities associated with conflict behavior in mice, Animal Behavior 14:44-49.
  • Hauschka, 1952, Whisker-eating mice, J. Hered. 43:77-80.

 

 

7. What are the malformations in vagina (Vaginal Septum/imperforate vagina) in C57BL/6J and BALB/cJ mice?

In C57BL/6JRj mice, the vaginal septum is well described:

  • Mice vagina is closed at birth and open at the age of 24 to 28 days, around the sexual maturity.
  • An opening defect is due to the recessive ipv mutation which causes a developmental defect in the caudal section of the Mullerian duct, leading the formation of a septum or an imperforated vagina.
  • Serious health complications (distension of the vagina, cervix and uterus) for the mouse and inability to reproduce.Animals submitted exhibited extreme distention of the abdomen. Differential diagnoses include abdominal (umbilical) abscessation, macerated fetuses, or neoplasia in these animals. A hypoplastic vagina opening can be observed on the affected animals. When the abdomen is opened, the uterine horns are markedly distended, thin walled, and translucent. Clear to slightly cloudy mucous is obtained when the walls are cut.

 

This defect was identified in 1976, with incidence of 4.0% in this strain. A Study in 2004 (Gearhart et al.) reported incidence of 11.3%, nearly triple the original reported incidence.

For comparison, incidence of vaginal septum in C57BL/6N females was determined and was found to be 1%.

Imperforate vagina in the mouse is believed to be inherited in a complex recessive manner.

An alternative could be working on the C57BL/6N less sensitive to this phenomenon of vaginal septum (Cf. “Differences between C57BL/6J and C57BL/6N”).

References

  • Gearhart et al. 2004, Increased Incidence of Vaginal Septum in C57BL/6J Mice Since 1976, Comparative Medicine, 54(4):  418-421
  • Eisen, 1989
  • Jubb et al.1985, Pathology of Domestic Animals. 3rd ed., Academic Press, Orlando
  • Cunliffe-Beamer and Feldman, 1976, Vaginal septa in mice: incidence, inheritance, and effect on reproductive performance. Lab Anim Sci 26:895-898
  • Green, 1975, Biology of the Laboratory Mouse, Dover Publications, New York.

 

 

8. What is malocclusion in the laboratory rodents?

The teeth of rodents grow continuously. Eruption of the incisors in young mice and rats occurs between days 10-12 of age. In mice, the normal rate of eruption (which equals the rate of wear, so that the incisors remain a constant size in adult mice) is approximately 2mm/week for the upper incisors and 2.8mm/week for the lower incisors. This results in a turnover of the entire tooth in 35-45 days.

Rodent teeth wear naturally by eating hard foods and gnawing behavior. In the laboratory, these conditions are mimicked by providing the animals with rodent chow formulated to be hard enough to wear the teeth.

Malocclusion should be the first disorder suspected when a mouse is smaller and thinner than its littermates at weaning.

Malocclusion is a dental disorder of many strains of laboratory rodents and is readily diagnosed by an oral examination. It is a misalignment of teeth or incorrect relation between the teeth of the two dental arches. The incisors overgrow because the mandibular and maxillary teeth are not normally aligned and do not properly occlude. Dental malocclusion affects incisors of rodents, but may also affect the molars, resulting in impaired chewing.

Malocclusions may be coupled with skeletal disharmony of the face, where the relations between the upper and lower jaws are not appropriate. Such skeletal disharmonies often distort sufferer's face shape, severely affect aesthetics of the face and may be coupled with mastication or speech problems. They can grow disproportionately, even punching walls mouth (palate, cheeks) and cause serious injury or even death of the animal.

If the growing teeth penetrate facial structures, it may also result in oral and facial abscesses and osteomyelitis. The standard recommendation for animals with malocclusion is euthanasia. When the malocclusion is later in onset and due to trauma, oral tumor formation, or other causes, it is possible to manage the treatment of a valuable mouse through a program of regular tooth trimming using blunt-tipped scissors, to prevent inadvertent oral trauma, and adding a provision of powdered diet.

References

  • Dontas et al. 2010, Malocclusion in aging Wistar rats, J Am Assoc Lab Anim Sci. 49: 22-6
  • JAX® NOTES Issue 489, Spring 2003.
  • Petznek et al. 2002, Reduced body growth and excessive incisor length in insertional mutants mapping to mouse Chromosome 13. Mammalian Genome; 13:504-509.
  • Peters and Balling, 1999, Teeth. Where and how to make them. Trends in Genetics; 15:59-65.
  • Miller, 1977, Genetic traumatic occlusion in the mouse. J Periodontal Res; 12:64-72.

 

 

9. What are the differences between BALB/c sublines?

Origin

Similarly, the original BALB/c strain separated into two major substrains (BALB/cJ and BALB/cByJ) back in 1935 (Potter et al. 1985, History of the BALB/c family, Curr Topics Microbiol Immunol. 122:1-5).

Genetic

Known genetic differences between these substrains include, in the BALB/cByJ strain:

  • Acadsdel-J (acyl-Coenzyme A dehydrogenase, short chain),
  • Ahrb-2 (aryl-hydrocarbon receptor),
  • Cdh23ahl [cadherin 23 (otocadherin)].

 

Although these strains are considered matched at the Major Histocompatibility Complex (MHC) (they have the H2d haplotype) and tissues can be transplanted between strains, the class 1b locus in BALB/cAnN and BALB/cByJ contains a deletion in Qa2 on Chromosome 17 (Flaherty et al. 1985, Characterization of a Q subregion gene in the murine major histocompatibility complex, Proc Natl Acad Sci U S A.; 82(5):1503-7; Mellor et al. 1985, Structure and expression of genes encoding murine Qa-2 class I antigens, Proc. Natl. Acad. Sci., USA 82:5920-4; Rogers et al. 1985, Qa2 Expression in BALB/c Sublines and a BALB/cLAC Tumor, Curr Top Microbiol Immunol.; 122: 43-9).

The genes controlling the Qa2 lymphocyte alloantigen was discovered by Lorraine Flaherty and her colleagues (Flaherty et al. 1985). These genes are a cluster of class I-like genes located to the right of H2d in the mouse major histocompatibility (MHC) complex.

For additional variations between BALB/c substrains maintained throughout the world see The BALB/c Mouse. Genetics and Immunology, M. Potter (ed.), Current Topics in a Microbiology and Immunology 122, Springer-Verlag, 1985. (Source: The Jackson Laboratory).

Phenotype

  • BALB/cByJ has a higher reproductive performance and is less aggressive than BALB/cJ.
  • BALB/cByJ females are good mothers and are commonly used as foster mothers.
  • BALB/cByJ mice have spontaneous dystrophic cardiac calcinosis, elevated free fatty acids, high triglyceride levels, and a number of hematologic abnormalities.
  • BALB/cJ is resistant to plasmacytoma induction in contrast to the striking susceptibility of other sublines

 

 

10. What are the differences between C57BL/6J and C57BL/6N?

Origin

C57BL/6N strain is an NIH (National Institute of Health) subline of C57BL/6. It was separated from C57BL/6J (The Jackson Laboratory) in 1951. 

Genetic

  • 5 SNP differences have been identified that distinguish C57BL/6J from C57BL/6ByJ and C57BL/6NJ. Both C57BL/6ByJ and C57BL/6NJ type as follows: 08-015199792-M (rs3709624) is C; 11-004367508-M (rs3659787) is A;13-041017317-M (rs3722313) is C; 15-057561875-M (rs3702158) is G; 19-049914266-M (rs3724876) is T. C57BL/6J types as follows: 08-015199792-M is T; 11-004367508-M is G; 13-041017317-M is T; 15-057561875-M is A; 19-049914266-M is G (Petkov and Wiles, 2005) (source: The Jackson Laboratory) (Petkov and Wiles, 2005).
  • Studies showed differences in the genetic polymorphism between the C57BL/6J and the C57BL/6N strain (Bothe et al. 2004; Tsang et al. 2005; Mekada et al. 2009; Zurita et al. 2010).
  • The C57BL/6N strain does not have the deletion in the Nnt gene that has been found in the C57BL/6J strain.
  • The C57BL/6N strain have the rd8 mutation (retinal degeneration 8), not found in the C57BL/6J strain.

Behavior

Differences exist in behavior between the C57BL/6J and the C57BL/6N strain (Matsuo et al. 2010): preference to ethanol, the conditioning fear, the motor coordination and the pain sensibility (Blum et al. 1982; Bryant et al. 2008); the locomotor activity is higher and the anxiety behavior is lower in the C57BL/6J strain; the inhibition bursts of terror is high in the C57BL/6N strain. The fear responses differ between the C57BL/6J and the C57BL/6N strain (Radulovic et al. 1998; Stiedl et al. 1999).

Physiology

The anesthetic effects on the cardiac functions differ between the C57BL/6J and the C57BL/6N strain (Roth et al. 2002) and the electroconvulsive tresholds also differ (Yang et al. 2003).

 

11. What are the characteristics of the immunodeficient strains?

Common name

Lou-nude

rat

NMRI-nu

mouse

BALB/c-nu

mouse

NOD-SCID

mouse

CB17-SCID

mouse

Beige

mouse

SCID-Beige

mouse

XID

mouse

Hair

No

No

No

Yes

Yes

Yes

Yes

Yes

Mature B cells

Present

Present

Present

Absent

Absent

Present

Absent

Absent

Mature T cells

Absent

Absent

Absent

Absent

Absent

Absent

Absent

Present

Dendritic cells

Present

Present

Present

Defective

Present

Present

Present

Present

Macrophages

Present

Present

Present

Defective

Present

Defective

Defective

Present

NK cells

Present

Present

Present

Defective

Present

Defective

Defective

Present

Complement

Present

Present

Present

Absent

Present

Present

Present

Present

Leakiness

N/A

N/A

N/A

Low

Low

Low

Low

 

Benefits

 

- Engraftment of human & mouse tumor cell lines

- Well published/ characterized

- Segregating genetic background improves hybrid vigor

- Hairless phenotype enhances assessment of tumor growth

 

- Engraftment of human & mouse tumor cell lines

- Well published/ characterized

- Uniform genetics improve reproducibility

- Hairless phenotype enhances assessment of tumor growth

 

- Adoptive transfer recipient for study of autoimmune type 1 diabetes

- Engrafts hematopoietic cancer cell lines

- Xenograft of some human tumors

 

 

 

 

- X-chromosomei-linked mutation xid

Availability

Yes

Yes

Yes

Yes

Yes

No

No

No

 

12. What is a NUDE strain?

Origin 

The first nude mouse appeared at the Virus Laboratory, Ruchill Hospital, Glasgow in 1962 in Dr. N.R. Grist laboratory. Dr. Grist sent the mutation to the Institute of Animal Genetics at Edinburgh for investigation. The mutation arose in a closed but not deliberately inbred albino stock. In December 1968, Dr. Ryggard obtained two heterozygous pairs (nu/+) mice from the Institute for Animal Genetics, Edinburgh, Scotland. 

In 1953 rats with nude characteristics appeared for the first time in an outbred hooded rat colony at the Rowett Research Institute, Aberdeen, Scotland. The mutation reappeared in the 1970s in the same outbred colony (May et al. 1977; Festing

et al. 1978). The autosomal recessive mutation is designated rnu for rowett nude. The “Institut Pasteur Lille” (IPL) acquired it with the collaboration of M. Capron with M. Bazin (1977). In 1993, l’IPL decided to transfer the nude mutation

on that Lou/M rat from nude rats of CESAL (CDTA) and from Lou/M rat by successive back cross. 

Genetic Data

The spontaneous nude mutation arises in the Foxn1 (forkhead box N1) gene which encodes the Foxn1 transcription factor (named also Whn: winged-helix-nude) with a DNA binding domain of the forkhead/winged-helix class. Foxn1 regulates the keratin gene expression and is required for the growth and the differenciation of thymic cells. The mutation introduces a frameshift and a premature stop codon (Hirasawa et al. 1998). The encoded protein is predicted to terminate upstream of the DNA-binding domain. 

For the mice, the nude mutation (nu) is on the chromosome 11. It is an autosomal and recessive mutation, a single base pair (G) deletion in exon 3.

For the rats, the nude mutation is called Rowett nude mutation (rnu) and is on the chromosome 10. In the rat rnu allele, a nonsense mutation in exon 8 of the whn gene was identified. The truncated whnrnu protein contains the DNA binding domain but lacks the 175 C-terminal amino acids of the wild-type protein (Schüddekopf et al. 1996; Hirasawa et al. 1998).

The rnu mutation in rats is analogue to the nude mutation in mice.

Mutation Phenotype

Foxn1 is required for a normal skin, hair and thymus development.

The nude mutation is associated with hairlessness and thymic aplasia:

  • A keratinization defect of the hair follicle and the epidermis give a nearly total hair absence with a transient downy hairs apparition. The mutation does not affect the hair formation but its rigidity (bends and breaks itself). Hair follicles are normal at birth, but keratinization is faulty and the hairs do not erupt. Epidermal keratinization also is faulty. Vibrissae are present in all fetuses at 16th day of gestation, but at birth the nude strains can be differentiated from heterozygote littermates by the appearance of the vibrissae. In the nude strains, the number of whiskers is less than in the normal littermates, and those which are present are bent and coiled.

 

  • With a disturbed protein, the primitive thymic cells cannot be differentiated in mature cells of the normal thymus (Festing et al. 1978, Balciunaite et al. 2002). The thymus is in a rudimentary form (Fossum et al. 1980; Vos et al. 1980) due to failure of development of the thymic anlage which arises from the ectoderm of the third pharyngeal pouch. The rudiment remains small and cystic. Another derivative of the third pharyngeal pouch, the parathyroid, is unaffected by the nude mutation. This mutation causes a severe impairment of the immune system by the thymic aplasia. The T lymphocytes mature in the thymus.Therefore, there is a low number of mature T lymphocytes (immunodeficiency) but the other immune cells are fonctionnal, not depending on thymus. There is no intrinsic defect for the T lymphocytes precursors. Nude strains are highly sensitive to several infections by bacterial, parasites and viral pathogens. In vivo assessments show that thymus-dependent immunity, including the response to thymus-dependent antigens, alloreactivity in graft rejection, and graft-versus-host reactivity, is lower than normal or absent in nude. 

 

  • Nude females have a mammary gland development defect and have incapacity to suckle their litters (Guillaumot, 1986; Militzer and Schwalenstöcker, 1996). Therefore, nude males are crossed with heterozygous females to maintain nude colonies.

 

  • Body growth rate, viability, and fertility are severely reduced.

 

  • Heterozygous Foxn1nu/Foxn1+ do not show partial expression of the nude phenotype.

 

13. What is the difference between hairless vs Nude strain?

 

Hairless

Nude

Gene

Dsg4 (exemple)

Foxn1 (always)

Mutation

hairless

nude

(rnu: rat; nu: mice)

Hair

No ( defective hair shafts)

No ( keratinization defect)

Thymus

Euthymic

Athymic

Immunity

Competent

Deficient

Reproduction

OK

Deficient (♀)

Conditions

Normal

Sanitary barrier = filter covers on cages, germfree isolators, sterilized materials/feed/water/bedding (autoclaving)

 

14. What is the difference between SCID vs Nude strain?

 

SCID

Nude

        Gene

Prkdc

Foxn1 (always)

      Mutation

Scid (severe combined immune deficiency)

nude

(rnu: rat; nu: mice)

         Hair

Yes

No

       Thymus

Rudimentary

Athymic

      Immunity

Deficient

Deficient

   T lymphocyte

No

No

   B lymphocyte

No

Yes

       NK cells

According to the background

Yes

   Complement

According to the background

Yes

 

 

15. What is the difference between CB17 SCID vs NOD SCID strain?

 

CB17

NOD

Mutation

Prkdcscid

Prkdcscid

T lymphocyte

No

No

B lymphocyte

No

No

NK cells

Yes

decreased

Complement

Yes

No

 

16. What are the differences between nude, hairless and SCID strain? 

 

BALB/c-nu

NMRI-nu

Lou/M-rnu

SDH-Dsg4

CB17-SCID

NOD SCID

T lymphocyte

No

No

No

Yes

No

No

B lymphocyte

Yes

Yes

Yes

Yes

No

No

NK cells

Yes

Yes

Yes

Yes

Yes

decreased

Complement

Yes

Yes

Yes

Yes

Yes

No

 

17. What are the differences between BP/2IcRj-BIOZZI vs other BIOZZI mice?

BP/2IcRj-Biozzi (Biozzi et al.) is also called HI.

The ABH strain is derived from the previous BP (or HI) strain. The ABH and BP strains derived (Liu et al. 1993).

Biozzi mice are marked by their high titre antibody responses following immunization with protein antigens.

 

BP/2IcRj

ABH

Meaning

Bonne productrice d’anicorps de type 2 (good producer of type 2 antibody)

Anti-Body High

Breeding

Inbred

Inbred

Histocompatibility

H2q

H2dq1

Color gene

Tyrc (c/c) albino

Tyrc (c/c) albino

Remarkable genes

Asthm1, Asthm2

Deletion ligand for TcR-V beta 6+ and TcR-V beta 8.1+ T cells; Mtv-7; Mls-1a

Model

Asthma

CNS autoimmune inflammatory diseases as EAE, multiple sclerosis

Life span/diseases

Bronchial hyperresponsiveness

Mean life span = 24.1 months ; at 13 months : 28% rheumatoid-like arthritis

Reference

Vargaftig, 1999, What can we learn from murine models of asthma? Clin Exp Allergy.; 29 (1): 9-13

Amor et al. 2005, Biozzi mice: of mice and human neurological diseases, J Neuroimmunol.; 165(1-2): 1-10

Avaibility

Yes

No