Use of a cDNA recombinant for the γ-subunit of mouse nerve growth factor to localize members of this multigene family near the TAM-1 locus on chromosome 7

Abstract

The gamma-subunit of mouse 7S nerve growth factor (gamma-NGF) is a member of a family of closely related serine proteases that includes kallikreins and tamases. We have isolated from a DBA/2J male submaxillary gland cDNA library a clone, pSM676, which codes for gamma-NGF. Sequence analysis of the clone shows that it codes for the C-terminal 138 amino acids of the protein plus 23 bases of the 3'-nontranslated portion of the message. The predicted amino acid sequence agrees with that determined by Thomas et al. (1) for the gamma-subunit of nerve growth factor from Swiss Webster mice except for the single, conservative substitution of glutamate for aspartate at amino acid 175. When used as a probe for Southern blot analysis, pSM676 hybridizes to at least twelve fragments of restricted mouse genomic DNA which correspond to several different serine protease genes. Using mouse-hamster hybrid cell lines and recombinant inbred strains of mice, we have demonstrated that all of the genes which show homology to pSM676 are located on mouse chromosome 7, clustered at or near the Tam-1 locus.

Molecular biology of tissue kallikrein

“…(1) The mechanisms involved in the concerted evolution of the tandemly linked gene family members. The mouse kallikrein genes have been shown to be tightly clustered on chromosome 7 (Mason et al, 1983;Howles et al, 1984). The rat genes appear clustered as well (D. Wines, J. Brady & R. MacDonald, unpublished work).…”

“…Estimates of the size of the family are based on the number of cross-hybridizing genes. The number of members may vary greatly among mammals: the mouse has 24 member genes (Evans et al, 1987), the rat 10 (Ashley & MacDonald, 1985b) to 17 (Gerald et al, 1986); and possibly the hamster as few as three (Howles et al, 1984). The size of the human gene family appears smaller than that of mouse and rat (Fukushima et al, 1985;Baker & Shine, 1985), but contains at least four distinct genes: kallikrein and an unidentified partial gene sequence (Fukushima et al, 1985;Baker & Shine, 1985), prostate-specific antigen (Watt et al, 1986;Lundwall & Lilja, 1987), and a characterized but unidentified gene termed hGK-1 (Schedlich et al, 1987).…”

Role of glandular kallikreins as growth factor processing enzymes: Structural and evolutionary considerations

“…The strongest evidence is the lower genomic copy number of kallikreins in mammals other than the mouse. Although the mouse contains more than 25 kallikrein genes [3], the rat contains only 8-10 genes [41], and the hamster has been reported to have only 2-3 kallikrein genes [42]. These reduced numbers would obviously not provide enough specificity for processing enzymes.…”

Localization of a New Prostate-specific Antigen-related Serine Protease Gene, KLK4 , Is Evidence for an Expanded Human Kallikrein Gene Family Cluster on Chromosome 19q13.3–13.4

“…The rat family, although in two clusters, is tightly linked at one locus spanning 480 kb on chromosome 1 (11,18,19). Similarly, the mouse kallikrein family has been localized to a single 310-kb locus on chromosome 7, a position that is analogous to the human KLK locus on chromosome 19 (4,12,20). Overall, these findings suggest that if there are more members of the human kallikrein gene family they should be localized within close proximity to the current KLK locus on chromosome 19q13.3-13.4.…”