Pathology of Genetically Engineered and Other Mutant Mice. Группа авторов

Figure 3.3 Current symbols assigned to a variety of unrelated genes originally published as p38. If one searches for the gene symbol p38 the results indicate numerous genes on different chromosomes that at one time were all called p38. The new names not only separate out the different genes but also reflect to a degree what is currently known about the gene function. By following the links you can obtain much more detail on each gene, the number and details on allelic mutations, and links to the original and many subsequent publications on the topic (MGI accessed 22 April 2020).

Table 3.3 Inbred strains of mice.

AdvantagesGenetic and phenotypic uniformity (smaller numbers needed)Well characterized (pathology and physiology)For most standard inbred strains >200 generationsIdeal controls (both biological and sequencing)Permits clear genetic mappingEnables identification of modifier genes

DisadvantagesNot as robust (smaller, lower reproductive performance [fecundity], shorter lifespan)Strain‐specific characteristics (deleterious mutations causing strain specific diseases)Expensive (when difficult to maintain)

UsesWidely used in all types of researchModels for human diseaseBackground for mice with spontaneous and induced mutations

Table 3.4 Inbred strain nomenclature.

C57BL/6J or C57BL/10J

C57BL is the parental strain name (since C57BL/6J is the actual strain name)

6 or 10 indicate the substrain line number (C57BL/10J are prone to serious heart disease not seen in C57BL/6J) [8]

J indicates the breeder (The Jackson Laboratory) of these substrains

C3H/HeJ or C3H/HeN

C3H is the strain generated by Strong from a cross of Bagg albino with DBA

He is the substrain from the W.E. Heston laboratory at the National Cancer Institute

J indicates the subline received from Heston then bred by The Jackson Laboratory

N indicates the substrain bred at the National Institutes of Health

      An inbred strain is designated in capital letters.

      A substrain is identified using a forward slash (/) after the strain name followed by a lab code of the strain breeder.

      Further substrains derived from the founder add to the end of the lab code of subsequent breeders without another forward slash.

      Note that C3H/HeJ has a mutation in the Tlr4 gene making it highly susceptible to gram negative bacterial infection while the C3H/HeN substrain is wildtype for Tlr4.

Figure 3.4 Nomenclature for hybrid stocks.

Table 3.5 Examples of inbred strain abbreviations.

129P3/J = 129P3

129S1/SvImJ = 129S1

A/HeJ = AHe

A/J = A

AKR/J = AK

BALB/cByJ = CByJ

BALB/cJ = C

C57BL = B

C57BL/6J = B6

C57BL/6JEi = B6Ei

C57BL/6NJ = B6NJ

C57BL/10J = B10

C57BR/cdJ = BR

C57L = L

CBA/CaJ = CBACa

CBA/J = CBA

C3H/HeJ = C3

C3HeB/FeJ = C3Fe

DBA/1J = D1

DBA/2J = D2

NZB/BINJ = NZB

NZW/LacJ = NZW

RIIIS/J = R3

SJL/J = SJL or J

SWR/J = SW

Table 3.6 F1 and F2 hybrid mice.

F1 hybrids	F2 hybrids
AdvantagesGenetic and phenotypic uniformityContains a 50 : 50 mix of both parental strainsHybrid vigorAccepts transplants of tissue from mice of either parental strain	AdvantagesHybrid vigorF2 hybrids do not have 50 : 50 mix but do have some mice in the population homozygous for some alleles and are valuable as a population for mutant gene mapping
DisadvantageNot self‐perpetuating	DisadvantagesNot self‐perpetuatingGenotype and phenotype NOT uniformParental strains most likely reject tissue transplants
UsesRadiation researchBehavioral researchBioassays of nutrients, drugs, pathogens, or hormonesTransplant recipientsBackground for transgenics and some deleterious mutations	UseControl for many targeted (“knockout”) mutations on a mixed B6; 129

Sibling breeding F1 hybrid mice for one generation produces an F2 hybrid population (Figure 3.4), and continued inbreeding after that eventually leads to the creation of recombinant inbred strains (see below). The F2 hybrid population also has hybrid vigor, but is distinct from the F1 hybrid population because meiosis has resulted in recombinations between the parental chromosomes such that there may be some homozygosity in a minority of the segregating alleles. This makes an F2 hybrid population a tremendous tool for mapping, especially for mapping recessive mutations. For example, if an interesting phenotype is observed in an inbred strain, such as an abnormal hair coat, hair interior defect (hid) in all AKR/J mice, these animals can be crossed with another inbred strain, such as BALB/cByJ, that has normal hair (Figure 3.5). As hid in this example is an autosomal recessive mutation, the obligate heterozygous F1 progeny of this cross will all have a normal hair coat. When these heterozygous progeny are intercrossed to create F2 hybrids, 25% of these mice are expected to have the abnormal hair phenotype. The genetic interval carrying the mutant sequence derives from AKR/J so by screening the DNA from the mutant and unaffected mice in the population